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PMID	17496232 ( )
Title	Mitochondrial nitric oxide in the signaling of cell integrated responses.
Abstract	Mitochondria are the specialized organelles for energy metabolism, but, as a typical example of system biology, they also activate a multiplicity of pathways that modulate cell proliferation and mitochondrial biogenesis or oppositely promote cell arrest and programmed cell death by a limited number of oxidative or nitrosative reactions. These reactions are influenced by matrix nitric oxide (NO) steady-state concentration, either from local production or by gas diffusion to mitochondria from the canonical sources. Likewise, in a range of approximately 30-200 nM, NO turns mitochondrial O(2) utilization down by binding to cytochrome oxidase and elicits a burst of superoxide anion and hydrogen peroxide that diffuses outside mitochondria. Depending on NO levels and antioxidant defenses, more or less H(2)O(2) accumulates in cytosol and nucleus, and the resulting redox grading contributes to dual activation of proliferating and proapoptotic cascades, like ERK1/2 or p38 MAPK. Moreover, these sequential activating pathways participate in rat liver and brain development and in thyroid modulation of mitochondrial metabolism and contribute to hypothyroid phenotype through complex I nitration. On the contrary, lack of NO disrupts pathways like S-nitrosylation or H(2)O(2) production and likewise is a gateway to disease in amyotrophic lateral sclerosis with superoxide dismutase 1 mutations or to cancer proliferation. Cordoba 2351, 1120 Buenos Aires, Argentina. carreras@ffyb.uba.ar

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Targets by SciMiner Summary

HUGO ID	Symbol	Target Name	#Occur	ActualStr
6871	MAPK1	mitogen-activated protein kinase 1	65	ERK \| MAPKs \| ERKs \| MAPK \| p38 \|
7872	NOS1	nitric oxide synthase 1 (neuronal)	35	NOS \| nNOS \| neuronal nitric oxide synthase \|
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	15	COX \|
11180	SOD2	superoxide dismutase 2, mitochondrial	11	manganese superoxide dismutase \| MnSOD \|
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	10	NF-kappaB \|
990	BCL2	B-cell CLL/lymphoma 2	10	Bcl-2 \| bcl 2 \|
11998	TP53	tumor protein p53	8	p53 \|
6877	MAPK3	mitogen-activated protein kinase 3	8	ERK1 \|
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	8	superoxide dismutase 1 \| SOD1 \| SOD \|
6881	MAPK8	mitogen-activated protein kinase 8	7	JNK \| JNK1 \| JNK-related \|
1516	CAT	catalase	6	catalase \|
19986	CYCS	cytochrome c, somatic	6	cytochrome c \|
2928	DMD	dystrophin (muscular dystrophy, Duchenne and Becker types)	4	dystrophin \|
6886	MAPK9	mitogen-activated protein kinase 9	4	SAPK \|
5232	HSPA1A	heat shock 70kDa protein 1A	4	HSPs \| HSP \| hsp70 \| Hsp70 \|
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	4	TNF-alpha \| tnf alpha \|
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	4	ap 1 \| AP-1 \|
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	3	Akt \| PKB \|
10436	RPS6KB1	ribosomal protein S6 kinase, 70kDa, polypeptide 1	2	p70 s6k \| S6k \|
576	APAF1	apoptotic peptidase activating factor 1	2	apoptotic protease activating factor 1 \|
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	2	caspase 3 \|
1784	CDKN1A	cyclin-dependent kinase inhibitor 1A (p21, Cip1)	2	p21 \|
2903	DLG4	discs, large homolog 4 (Drosophila)	2	PSD95 \| psd95 \|
2874	NQO1	NAD(P)H dehydrogenase, quinone 1	2	nadh dehydrogenase \|
9175	POLD1	polymerase (DNA directed), delta 1, catalytic subunit 125kDa	1	cdc2 \|
29884	UBASH3B	ubiquitin associated and SH3 domain containing, B	1	p70 \|
992	BCL2L1	BCL2-like 1	1	bcl xl \|
6843	MAP2K3	mitogen-activated protein kinase kinase 3	1	MKK3 \|
6848	MAP3K1	mitogen-activated protein kinase kinase kinase 1	1	MEKK \|
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	1	nitric oxide synthase \|
2432	CSF1	colony stimulating factor 1 (macrophage)	1	macrophage colony stimulating factor \|
1511	CASP9	caspase 9, apoptosis-related cysteine peptidase	1	caspase 9 \|
9567	PSMD9	proteasome (prosome, macropain) 26S subunit, non-ATPase, 9	1	p27 \|
1773	CDK4	cyclin-dependent kinase 4	1	cdk4 \|
5438	IFNG	interferon, gamma	1	IFN-gamma \|
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	1	GAPDH \|
7889	NOX1	NADPH oxidase 1	1	Nox1 \|
12435	TXN	thioredoxin	1	Trx \|
4827	HBB	hemoglobin, beta	1	hemoglobin \|
17169	PRDX4	peroxiredoxin 4	1	thioredoxin peroxidase \|
11920	FAS	Fas (TNF receptor superfamily, member 6)	1	Fas \|
784	ATF2	activating transcription factor 2	1	ATF-2 \|
6915	MB	myoglobin	1	myoglobin \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
6877	MAPK3	mitogen-activated protein kinase 3	ERK1	2.7	to dual activation of proliferating and proapoptotic cascades like ERK1/2 ERK1 2 or p38 MAPK
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	of proliferating and proapoptotic cascades like ERK1/2 ERK1 2 or p38 MAPK
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	proliferating and proapoptotic cascades like ERK1/2 ERK1 2 or p38 MAPK
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	3.7	Transcriptional increase of neuronal nitric oxide synthase (nNOS) nNOS determines extensive binding to complex I and IV and contributes
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	3.7	3 3' 5-triiodothyronine (T T 3 levels there is increased nNOS transcription translation and translocation into mitochondria resulting in high mitochondrial
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	transcription translation and translocation into mitochondria resulting in high mitochondrial NOS (mtNOS) mtNOS activity and increased nitric oxide (NO), NO ONOO
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	MW molecular weight MnSOD manganese superoxide dismutase 2D two dimensional
6877	MAPK3	mitogen-activated protein kinase 3	ERK1	2.7	low NO and H 2 O 2 levels activate ERK1/2, ERK1 2 resulting in cyclin D 1 -increased expression and proliferation
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	higher NO ONOO and H 2 O 2 levels activate p38 MAPK which regulates cyclin D 1 expression negatively resulting in
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	NO ONOO and H 2 O 2 levels activate p38 MAPK which regulates cyclin D 1 expression negatively resulting in cell
6871	MAPK1	mitogen-activated protein kinase 1	MAPKs	2.2	Representative Western blot of cyclin D 1 and MAPKs in tumoral cells (P07) P07 and in lysates of postnatal
11998	TP53	tumor protein p53	p53	1.6	programmed cell death via apoptotic protease-activating factor-1 and activation of p53
11998	TP53	tumor protein p53	p53	1.6	Increased NO and ONOO result in DNA damage p53 accumulation increased Bax/Bcl-2, Bax Bcl-2 cytochrome c (cyt cyt c
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.3	ONOO result in DNA damage p53 accumulation increased Bax/Bcl-2, Bax Bcl-2 cytochrome c (cyt cyt c release and caspase activation
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	as resulting from its high-affinity binding to cytochrome oxidase (COX), COX the final electron acceptor ( 19
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	and O 2 is catalyzed by nitric oxide synthases (NOS) NOS ( 92
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	There exist three canonical isoforms neuronal (NOS NOS I or nNOS inducible (NOS NOS II and endothelial (NOS
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	3.7	There exist three canonical isoforms neuronal (NOS NOS I or nNOS inducible (NOS NOS II and endothelial (NOS NOS III and
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	canonical isoforms neuronal (NOS NOS I or nNOS inducible (NOS NOS II and endothelial (NOS NOS III and a significant number
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	I or nNOS inducible (NOS NOS II and endothelial (NOS NOS III and a significant number of spliced and posttranslationally modified
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	In addition new isoforms or mitochondrial variants of NOS (mtNOS) mtNOS were recently described in rat liver ( 60
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	( 119 mtNOS is bound to mitochondrial PDZ domains of COX ( 57 103 and to complex I ( 57 thus
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	as extreme hypoxia mitochondrial NO could come either from stimulated NOS ( 116 142 or from the reduction of nitrite by
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	( 116 142 or from the reduction of nitrite by COX ( 39
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	NOS I and III ( 45 82 are constitutively expressed in
2903	DLG4	discs, large homolog 4 (Drosophila)	PSD95	1.3	in cell membrane (caveolin) caveolin and in synaptic vesicles (PSD95) PSD95 in skeletal and cardiac muscles (dystrophin) dystrophin and to heat
2928	DMD	dystrophin (muscular dystrophy, Duchenne and Becker types)	dystrophin	1.0	synaptic vesicles (PSD95) PSD95 in skeletal and cardiac muscles (dystrophin) dystrophin and to heat shock protein (HSP) HSP 90 or 70
5232	HSPA1A	heat shock 70kDa protein 1A	HSP	0.9	cardiac muscles (dystrophin) dystrophin and to heat shock protein (HSP) HSP 90 or 70 chaperones ( 79
2928	DMD	dystrophin (muscular dystrophy, Duchenne and Becker types)	dystrophin	1.0	decreased (caveolin-NOS) caveolin-NOS enzyme activity 2 modified subcellular traffic (dystrophin dystrophin impedes NOS I traffic to mitochondria ( 76 and 3
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	caveolin-NOS enzyme activity 2 modified subcellular traffic (dystrophin dystrophin impedes NOS I traffic to mitochondria ( 76 and 3 participation in
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	Constitutive NOS are activated by Ca pulses after activation of cell surface
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	surface receptors by effectors like bradykinin or acetylcholine (endothelial endothelial NOS III or excitatory amino acids like glutamate (neuronal neuronal synaptic
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	III or excitatory amino acids like glutamate (neuronal neuronal synaptic NOS I ( 45
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	NOS I and III are characterized by fast and transient responses
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	In contrast NOS II is not constitutive and does not depend on Ca
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	is not constitutive and does not depend on Ca concentration NOS II gene expression is modulated by inflammatory mediators like cytokines
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	0.8	II gene expression is modulated by inflammatory mediators like cytokines TNF-alpha IFN-gamma and LPS that activate transcription factors like NF-kappaB or
5438	IFNG	interferon, gamma	IFN-gamma	0.8	gene expression is modulated by inflammatory mediators like cytokines TNF-alpha IFN-gamma and LPS that activate transcription factors like NF-kappaB or AP-1
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	AP-1	1.0	IFN-gamma and LPS that activate transcription factors like NF-kappaB or AP-1 ( 59
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	cytokines TNF-alpha IFN-gamma and LPS that activate transcription factors like NF-kappaB or AP-1 ( 59
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	The activities of classic NOS isoforms are able to sustain NO cytosolic concentrations large enough
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	Therefore mitochondrial NO coming from classic cytosolic NOS results in a considerably lower concentration ~20-100 nM ( 18
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	however it may increase by fivefold after induction of inducible NOS in endotoxemia ( 14
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	is noteworthy that changes in the expression and activities of NOS isoforms particularly of intra-mtNOS will be followed by significant variations
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	( 25 NO reversibly binds to Cu B center of COX and consequently inhibits electron transfer to O 2 and mitochondrial
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	concentrations 50-100 nM NO inhibits by half the activity of COX ( 108 110
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	represents a simple competition between NO and O 2 for COX the formation of the complex between COX and NO was
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	O 2 for COX the formation of the complex between COX and NO was followed by the authors after addition of
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	The time scale for the inhibition of COX by NO is given by k NOon x NO at
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	Therefore the fast inhibition of COX by NO is completely compatible with a direct competition between
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	with a direct competition between NO and O 2 for COX at the steady state and in the presence of NO
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	Eq 2 which describes a simple linear competitive inhibition of COX by NO with an inhibition constant ( K i given
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	These calculations are useful for isolated COX although they should be modified to include additional NO effects
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	Accordingly NO inhibits COX and increases the reduction levels of the components of the
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	chain including ubiquinol and ubisemiquinone on the substrate side of COX and reacts directly with ubiquinol to produce nitroxyl anion (NO
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	In the presence of mitochondrial manganese superoxide dismutase (MnSOD), MnSOD most of O 2 is dismutated to H 2 O
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	dismutates to H 2 O 2 a reaction catalized by MnSOD ( reactions 4 and 5
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	in mitochondrial metabolism will depend on NO concentration and on MnSOD level
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	2.2	20-fold NO utilization in contrast addition of superoxide dismutase (SOD) SOD decreases NO utilization and prolongs its mean life and increases
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	decays by reaction 4 and 2 depending on NO and MnSOD concentrations mitochondrial utilization of NO involves the formation of H
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	Our underlying proposal is that grading expression and activities of NOS isoforms and the concentration of matrix NO modulate H 2
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	As described in cell transformation ( 71 concomitant changes in MnSOD have two effects to increase cytosolic H 2 O 2
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	Cu ZnSOD whereas in mitochondria the reaction is catalyzed by MnSOD
12435	TXN	thioredoxin	Trx	1.0	(GPx; GPx reactions 6 and 7 and thioredoxin peroxidase (Trx; Trx reaction 8 are preferentially distributed in cytosol and peroxisomes
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	process including the concentration and activities of mtNOS cytosolic classic NOS isoforms MnSOD catalase and peroxidases
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	the concentration and activities of mtNOS cytosolic classic NOS isoforms MnSOD catalase and peroxidases
7889	NOX1	NADPH oxidase 1	Nox1	0.3	( 7 showed that transfection of oxidase Nox1 to NIH/3T3 NIH 3T3 fibroblasts which increases cell H 2
6871	MAPK1	mitogen-activated protein kinase 1	MAPKs	2.2	and H 2 O 2 are confluent on modulation of MAPKs and cyclin D 1
6871	MAPK1	mitogen-activated protein kinase 1	MAPKs	2.2	MAPKs including SAPK/JNK, SAPK JNK p38 MAPK and ERK are believed
6886	MAPK9	mitogen-activated protein kinase 9	SAPK	2.2	MAPKs including SAPK/JNK, SAPK JNK p38 MAPK and ERK are believed to be redox-dependent
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	MAPKs including SAPK/JNK, SAPK JNK p38 MAPK and ERK are believed to be redox-dependent biomolecules
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	MAPKs including SAPK/JNK, SAPK JNK p38 MAPK and ERK are believed to be redox-dependent biomolecules that
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	MAPKs including SAPK/JNK, SAPK JNK p38 MAPK and ERK are believed to be redox-dependent biomolecules that modulate
6871	MAPK1	mitogen-activated protein kinase 1	ERK	2.2	MAPKs including SAPK/JNK, SAPK JNK p38 MAPK and ERK are believed to be redox-dependent biomolecules that modulate cell proliferation
6871	MAPK1	mitogen-activated protein kinase 1	ERKs	2.2	ERKs stimulate cell proliferation and induction of active cyclin D 1
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	AP-1	1.0	cyclin D 1 by different mechanisms including the enhancement of AP-1 activity
6871	MAPK1	mitogen-activated protein kinase 1	ERKs	2.2	moderate elevation of intracellular Ca and leads to activation of ERKs and potentiates cell division functionally blocking Ca or inhibiting calmodulin
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	potentiates cell division functionally blocking Ca or inhibiting calmodulin or MAPK activities prevents ERK activation and antagonizes the mitogenic effect of
6871	MAPK1	mitogen-activated protein kinase 1	ERK	2.2	functionally blocking Ca or inhibiting calmodulin or MAPK activities prevents ERK activation and antagonizes the mitogenic effect of NO ( 90
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	On the other hand p38 SAPK transcriptionally downregulates cyclin D 1
6886	MAPK9	mitogen-activated protein kinase 9	SAPK	2.2	On the other hand p38 SAPK transcriptionally downregulates cyclin D 1
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	cyclin D 1 activity and expression the former by activating p38 pathway ( 37
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	8 who reported a temporal inverse correlation between activation of p38 MAPK and cyclin D 1 content during liver development or
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	who reported a temporal inverse correlation between activation of p38 MAPK and cyclin D 1 content during liver development or liver
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	Similarly NO activates p38 MAPK and suppresses proliferation through the activation of JAK2-STAT5 and
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	Similarly NO activates p38 MAPK and suppresses proliferation through the activation of JAK2-STAT5 and cyclin
1773	CDK4	cyclin-dependent kinase 4	cdk4	0.3	through the activation of JAK2-STAT5 and cyclin D 1 /cdk4 cdk4 ( 70
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	signal pathways involving both production of NO and activation of p38 MAPK pathway ( 93
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	pathways involving both production of NO and activation of p38 MAPK pathway ( 93
6871	MAPK1	mitogen-activated protein kinase 1	MAPKs	2.2	57 attempted to connect oxidative stress and NO levels to MAPKs D cyclins and cell proliferation
29884	UBASH3B	ubiquitin associated and SH3 domain containing, B	p70	0.3	O 2 acts as a messenger in growth factor-induced p70(S6k) p70 S6k signaling pathway in mouse epidermal cells which plays an
10436	RPS6KB1	ribosomal protein S6 kinase, 70kDa, polypeptide 1	S6k	0.3	2 acts as a messenger in growth factor-induced p70(S6k) p70 S6k signaling pathway in mouse epidermal cells which plays an important
6877	MAPK3	mitogen-activated protein kinase 3	ERK1	2.7	Finally our group ( 2 observed ERK1/2 ERK1 2 activation in brain mitochondria by very low concentrations of
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	redox effect on the protein or actions on ERK-MEK (MAPK MAPK kinase interactions
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	In this way it was proposed that duration of MAPK activation determines whether a stimulus produces proliferation or differentiation (
6877	MAPK3	mitogen-activated protein kinase 3	ERK1	2.7	factor induced only a transient activation of MEK and ERK1/2 ERK1 2 and 50% increase in cell proliferation whereas prolonged stimulation
6877	MAPK3	mitogen-activated protein kinase 3	ERK1	2.7	The findings gain significance considering that ERK1/2 ERK1 2 are activated by ROS ( 134
1784	CDKN1A	cyclin-dependent kinase inhibitor 1A (p21, Cip1)	p21	0.6	and to resulting changes in cell cycle regulators such as p21 p27 cyclins and retinoblastoma protein
9567	PSMD9	proteasome (prosome, macropain) 26S subunit, non-ATPase, 9	p27	0.3	to resulting changes in cell cycle regulators such as p21 p27 cyclins and retinoblastoma protein
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	For instance activation of p38 MAPK and cell cycle arrest may finally progress to apoptosis
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	For instance activation of p38 MAPK and cell cycle arrest may finally progress to apoptosis in
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	apoptosis in the presence of NO which may activate the p38 MAPK pathway
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	in the presence of NO which may activate the p38 MAPK pathway
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	In accord the p38 inhibitor SB-203580 blocks proapoptotic effects of NO in SH-SY5Y neurons
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	The activating NO effects and p38 MAPK signaling probably result in Bax translocation to mitochondria a
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	The activating NO effects and p38 MAPK signaling probably result in Bax translocation to mitochondria a well-known
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	microM H 2 O 2 causes a rapid activation of p38 MAPK cascade with phosphorylation of MKK3/6 MKK3 6 and p38
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	H 2 O 2 causes a rapid activation of p38 MAPK cascade with phosphorylation of MKK3/6 MKK3 6 and p38 MAPK
6843	MAP2K3	mitogen-activated protein kinase kinase 3	MKK3	2.2	rapid activation of p38 MAPK cascade with phosphorylation of MKK3/6 MKK3 6 and p38 MAPK and activating transcription factors (ATF)-1 ATF
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	p38 MAPK cascade with phosphorylation of MKK3/6 MKK3 6 and p38 MAPK and activating transcription factors (ATF)-1 ATF -1 (cAMP cAMP
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	MAPK cascade with phosphorylation of MKK3/6 MKK3 6 and p38 MAPK and activating transcription factors (ATF)-1 ATF -1 (cAMP cAMP response
784	ATF2	activating transcription factor 2	ATF-2	1.2	factors (ATF)-1 ATF -1 (cAMP cAMP response element-binding protein and ATF-2
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	and were cancelled by N -acetylcysteine or SB-203580 a specific p38 MAPK inhibitor
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	were cancelled by N -acetylcysteine or SB-203580 a specific p38 MAPK inhibitor
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	that H 2 O 2 -induced cellular injury depends on JNK activation
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	In this case also p38 and ERK were activated by H 2 O 2 however
6871	MAPK1	mitogen-activated protein kinase 1	ERK	2.2	In this case also p38 and ERK were activated by H 2 O 2 however only JNK-related
6881	MAPK8	mitogen-activated protein kinase 8	JNK-related	2.7	ERK were activated by H 2 O 2 however only JNK-related injuring effects were inhibited by the MEK inhibitor PD-98059
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	Moreover JNK phosphorylation of p53 is important for the stabilization of proapoptotic
11998	TP53	tumor protein p53	p53	1.6	Moreover JNK phosphorylation of p53 is important for the stabilization of proapoptotic p53 protein (
11998	TP53	tumor protein p53	p53	1.6	phosphorylation of p53 is important for the stabilization of proapoptotic p53 protein ( 28
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	Early activation of p38 MAPK and ERK does not seem to be dependent on
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	Early activation of p38 MAPK and ERK does not seem to be dependent on cytotoxic
6871	MAPK1	mitogen-activated protein kinase 1	ERK	2.2	Early activation of p38 MAPK and ERK does not seem to be dependent on cytotoxic factors like
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	suggest that physiological H 2 O 2 -dependent activation of p38 MAPK may proceed many steps before a significant Ca release
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	that physiological H 2 O 2 -dependent activation of p38 MAPK may proceed many steps before a significant Ca release from
6886	MAPK9	mitogen-activated protein kinase 9	SAPK	2.2	stores and that Ca -dependent tyrosine kinase-induced activation of SAPK/JNK SAPK JNK reflects the progression of cell injury ( 73
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	and that Ca -dependent tyrosine kinase-induced activation of SAPK/JNK SAPK JNK reflects the progression of cell injury ( 73
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	The main mitochondrial antioxidant defense is MnSOD
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	2.2	At the same SOD level the production of ONOO (and and concurrent nitration at
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	2.2	Dismutation of O 2 by SOD proceeds with an order of magnitude lower than formation of
5232	HSPA1A	heat shock 70kDa protein 1A	HSPs	0.9	effects include S -nitrosylation and inhibition of caspases increase of HSPs and Bcl-2 and activation of Akt/PKB, Akt PKB which induces
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.3	S -nitrosylation and inhibition of caspases increase of HSPs and Bcl-2 and activation of Akt/PKB, Akt PKB which induces cytoprotective gene
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	Akt	0.5	caspases increase of HSPs and Bcl-2 and activation of Akt/PKB, Akt PKB which induces cytoprotective gene expression through NF-kappaB activation (
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	PKB	0.5	increase of HSPs and Bcl-2 and activation of Akt/PKB, Akt PKB which induces cytoprotective gene expression through NF-kappaB activation ( 85
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	of Akt/PKB, Akt PKB which induces cytoprotective gene expression through NF-kappaB activation ( 85
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.3	hand proapoptotic effects of NO include inhibition of NF-kappaB decreased Bcl-2 expression ( 87 -89 118 and increased p53 expression both
11998	TP53	tumor protein p53	p53	1.6	NF-kappaB decreased Bcl-2 expression ( 87 -89 118 and increased p53 expression both by NO-mediated inhibition of proteasome degradation and by
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	the other hand proapoptotic effects of NO include inhibition of NF-kappaB decreased Bcl-2 expression ( 87 -89 118 and increased p53
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	3.7	levels of 3 3' 5-triiodothyronine (T T 3 in hypothyroidism nNOS mRNA increased by threefold and nNOS translocation to mitochondria was
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	3.7	T 3 in hypothyroidism nNOS mRNA increased by threefold and nNOS translocation to mitochondria was favored with concomitant increase of mtNOS
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	3.7	Two effects emerged from nNOS confinement
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	consumption was more sensitive to L -arginine and to the NOS inhibitor N -monomethyl-L -arginine indicating the modulation of O 2
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	Mitochondrial redox contribution to the activation of MAPK cascades was also confirmed in the hypothyroid model
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	2 O 2 and peroxynitrite with the concomitant activation of p38 MAPK and the inactivation of ERK1/2 ERK1 2
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	O 2 and peroxynitrite with the concomitant activation of p38 MAPK and the inactivation of ERK1/2 ERK1 2
6877	MAPK3	mitogen-activated protein kinase 3	ERK1	2.7	concomitant activation of p38 MAPK and the inactivation of ERK1/2 ERK1 2
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	As shown before this MAPK pattern is consistent with cell cycle arrest and inhibition of
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	A similar effect of a NOS inhibitor N -nitro-L -arginine methyl ester ( L -NAME or
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	hypothyroid cell signaling back to control status indicates that differential MAPK activation and cyclin D 1 expression should not depend on
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	3.7	of complex I inhibition by NO-ONOO overproduced by increased translocated nNOS (mtNOS) mtNOS
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	3.7	It is interesting that lack of T 3 stimulates nNOS gene expression suggesting the existence of a tonic gene inhibition
6871	MAPK1	mitogen-activated protein kinase 1	ERK	2.2	cell types and its expression is positively regulated by the ERK pathway and antagonized by stress-activated p38 MAPK cascade ( 84
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	positively regulated by the ERK pathway and antagonized by stress-activated p38 MAPK cascade ( 84
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	regulated by the ERK pathway and antagonized by stress-activated p38 MAPK cascade ( 84
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	liver development cyclin D 1 content is inversely related to p38 MAPK activity which in turn may be regulated by ROS
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	development cyclin D 1 content is inversely related to p38 MAPK activity which in turn may be regulated by ROS (
9175	POLD1	polymerase (DNA directed), delta 1, catalytic subunit 125kDa	cdc2	1.3	by inhibition of cyclin D 1 or by inhibition of cdc2 (cyclin cyclin E and A pathways ( 104
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	observed that modulation of mtNOS and subsequent redox changes regulate MAPK cascades and cell cycle regulatory proteins in the sequence of
6877	MAPK3	mitogen-activated protein kinase 3	ERK1	2.7	and high cyclin D 1 expression associated with high ERK1/2 ERK1 2 and low p38 MAPK activities
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	1 expression associated with high ERK1/2 ERK1 2 and low p38 MAPK activities
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	expression associated with high ERK1/2 ERK1 2 and low p38 MAPK activities
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	2 O 2 levels by controlled treatment with scavengers or NOS inhibitors like N -acetylcysteine glutathione or L -NAME increased proliferation
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	Moreover isolated hepatocyte proliferation rate may be modulated by MAPK inhibitors or stimulators like U-0126 (MEK MEK inhibitor SB-202190 (p38
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	inhibitors or stimulators like U-0126 (MEK MEK inhibitor SB-202190 (p38 p38 inhibitor or anisomycin (p38 p38 activator suggesting that hepatocyte proliferation
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	(MEK MEK inhibitor SB-202190 (p38 p38 inhibitor or anisomycin (p38 p38 activator suggesting that hepatocyte proliferation signaling is related to a
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.3	that cleave specific aspartate residues in other regulatory proteins like Bcl-2 Bax and MEKK (for for review see Ref 83
6848	MAP3K1	mitogen-activated protein kinase kinase kinase 1	MEKK	2.2	aspartate residues in other regulatory proteins like Bcl-2 Bax and MEKK (for for review see Ref 83
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	0.8	In the extrinsic pathway binding of membrane ligands like TNF-alpha and Fas to membrane receptors triggers the activation of caspases
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	0.6	the extrinsic pathway binding of membrane ligands like TNF-alpha and Fas to membrane receptors triggers the activation of caspases and the
11998	TP53	tumor protein p53	p53	1.6	For instance proapoptotic p53 protein induces gene transcription of redox-related genes encoding proteins that
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	NO induces apoptotic cell death with the activation of JNK/SAPK JNK SAPK and p38 MAPK and caspase 3 or inactivation of
6886	MAPK9	mitogen-activated protein kinase 9	SAPK	2.2	induces apoptotic cell death with the activation of JNK/SAPK JNK SAPK and p38 MAPK and caspase 3 or inactivation of NF-kappaB.
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	cell death with the activation of JNK/SAPK JNK SAPK and p38 MAPK and caspase 3 or inactivation of NF-kappaB.
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	death with the activation of JNK/SAPK JNK SAPK and p38 MAPK and caspase 3 or inactivation of NF-kappaB.
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	In this way increased inducible NOS expression and NO production act as a negative regulatory feedback
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	NO production act as a negative regulatory feedback modulator of NF-kappaB activity ( 102
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	The stimulation or inhibition of NF-kappaB may be related to proliferative or apoptotic effects
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	NF-kappaB is activated by several agents including cytokines oxidant free radicals
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	Inappropriate activation of NF-kappaB has been linked to inflammatory events associated with autoimmune arthritis
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	In contrast complete and persistent inhibition of NF-kappaB has been linked directly to apoptosis inappropriate immune cell development
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.3	gene is associated with embryo lethality many antiapoptotic pathways like Bcl-2 are induced by NF-kappaB.
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	Disruption of the NF-kappaB gene is associated with embryo lethality many antiapoptotic pathways like
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	have been developed in cancer treatment including inhibition of the NF-kappaB pathway ( 144
11998	TP53	tumor protein p53	p53	1.6	the result of DNA damage which induces the accumulation of p53
11998	TP53	tumor protein p53	p53	1.6	NO-mediated p53 accumulation induces cell cycle arrest by p21 upregulation or apoptosis
1784	CDKN1A	cyclin-dependent kinase inhibitor 1A (p21, Cip1)	p21	0.6	NO-mediated p53 accumulation induces cell cycle arrest by p21 upregulation or apoptosis by increase in Bax/Bcl-xL, Bax Bcl-xL cytochrome
5232	HSPA1A	heat shock 70kDa protein 1A	Hsp70	0.9	antiapoptotic genes like that of heme oxygenase ( 127 and Hsp70 which protects hepatocytes from apoptosis induced by oxidative and nitrative
4827	HBB	hemoglobin, beta	hemoglobin	1.0	Likewise in sickle cell anemia the sickle cell hemoglobin is deficient in the intramolecular and intermolecular transfer of NO
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	2.7	and 10-20% of cases are due to mutations in the SOD1 gene ( 122 123
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	2.7	Considering that SOD1 mutations lead to an increase of the denitrosylase activity of
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	0.3	of proteins that are regulated by this mechanism (like like GAPDH and that increased denitrosylase activity is a toxic gain of
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	2.7	increased denitrosylase activity is a toxic gain of function of SOD1 mutants
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	the mitochondrial field we previously reported the existence of defective NOS and mtNOS in mitochondria from tumor cells ( 58
6877	MAPK3	mitogen-activated protein kinase 3	ERK1	2.7	O 2 yields high proliferation rate and activation of ERK1/2, ERK1 2 a pattern resembling that shown in embryonic development (
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	Because proapoptotic p38 or JNK1/2 JNK1 2 did not become phosphorylated we surmise
6881	MAPK8	mitogen-activated protein kinase 8	JNK1	2.7	Because proapoptotic p38 or JNK1/2 JNK1 2 did not become phosphorylated we surmise the results are
6871	MAPK1	mitogen-activated protein kinase 1	MAPKs	2.2	setting H 2 O 2 ss with differential activation of MAPKs Akt and cyclin D In this sense very low NO
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	Akt	0.5	H 2 O 2 ss with differential activation of MAPKs Akt and cyclin D In this sense very low NO inhibits
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	0.9	and cyclin D In this sense very low NO inhibits COX and determines low H 2 O 2 yield
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase 1	1.0	on the contrary lack of no disrupts pathways like s nitrosylation or h 2 o 2 production and likewise is a gateway to disease in amyotrophic lateral sclerosis with superoxide dismutase 1 mutations or to cancer proliferation.
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	peroxynitrite; hydrogen peroxide; mitochondrial nitric oxide synthase; mitogen activated protein kinase
7872	NOS1	nitric oxide synthase 1 (neuronal)	neuronal nitric oxide synthase	1.0	transcriptional increase of neuronal nitric oxide synthase nnos determines extensive binding to complex i and iv and contributes to hypothyroid phenotype.
11180	SOD2	superoxide dismutase 2, mitochondrial	manganese superoxide dismutase	1.0	mw molecular weight; mnsod manganese superoxide dismutase; 2d two dimensional.
576	APAF1	apoptotic peptidase activating factor 1	apoptotic protease activating factor 1	1.0	no and h 2 o 2 release and activation of intrinsic programmed cell death via apoptotic protease activating factor 1 and activation of p53.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	increased no and onoo result in dna damage p53 accumulation increased bax/bcl 2 cytochrome c cyt c release and caspase activation.
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	increased no and onoo result in dna damage p53 accumulation increased bax/bcl 2 cytochrome c cyt c release and caspase activation.
2903	DLG4	discs, large homolog 4 (Drosophila)	psd95	1.0	these enzymes are bound to anchoring proteins in cell membrane caveolin and in synaptic vesicles psd95 in skeletal and cardiac muscles dystrophin and to heat shock protein hsp 90 or 70 chaperones 79 .
2928	DMD	dystrophin (muscular dystrophy, Duchenne and Becker types)	dystrophin	1.0	these enzymes are bound to anchoring proteins in cell membrane caveolin and in synaptic vesicles psd95 in skeletal and cardiac muscles dystrophin and to heat shock protein hsp 90 or 70 chaperones 79 .
2928	DMD	dystrophin (muscular dystrophy, Duchenne and Becker types)	dystrophin	1.0	the interaction with these proteins may involve different effects: 1 increased hsp90 nos or decreased caveolin nos enzyme activity 2 modified subcellular traffic dystrophin impedes nos i traffic to mitochondria 76 and 3 participation in ubiquitination and degradation 54 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	in contrast nos ii is not constitutive and does not depend on ca concentration; nos ii gene expression is modulated by inflammatory mediators like cytokines tnf alpha ifn gamma and lps that activate transcription factors like nf kappab or ap 1 59 .
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	ap 1	1.0	and does not depend on ca concentration; nos ii gene expression is modulated by inflammatory mediators like cytokines tnf alpha ifn gamma and lps that activate transcription factors like nf kappab or ap 1 59 .
6915	MB	myoglobin	myoglobin	1.0	most no binds to cytosolic compounds like myoglobin 35 111 .
11180	SOD2	superoxide dismutase 2, mitochondrial	manganese superoxide dismutase	1.0	in the presence of mitochondrial manganese superoxide dismutase mnsod most of o 2 is dismutated to h 2 o 2 which is freely diffusible to cytosol.
2874	NQO1	NAD(P)H dehydrogenase, quinone 1	nadh dehydrogenase	1.0	cordingly at 0.3 0.5 microm no inhibits electron transfer between cytochromes b and c 1 in the respiratory chain 108 111 whereas relatively prolonged 0.5 1 microm no exposure selectively inhibits the nadh dehydrogenase activity at mitochondrial complex i in intact cells 50 and isolated mitochondria 120 a hallmark of neurodegenerative experimental or clinical entities like parkinson disease.
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	in agreement supplementation of submitochondrial particles with complex i or complex ii substrates increases by 10 to 20 fold no utilization; in contrast addition of superoxide dismutase sod decreases no utilization and prolongs its mean life and increases h 2 o 2 110 .
1516	CAT	catalase	catalase	1.0	because peroxisomes contain the highest concentration of catabolizing catalase mitochondria with very low levels of degrading enzymes are accepted as the main source of o 2 species 17 33 .
17169	PRDX4	peroxiredoxin 4	thioredoxin peroxidase	1.0	otherwise enzymes that catabolize h 2 o 2 catalase gluthatione peroxidase gpx; reactions 6 and 7 and thioredoxin peroxidase trx; reaction 8 are preferentially distributed in cytosol and peroxisomes.
1516	CAT	catalase	catalase	1.0	otherwise enzymes that catabolize h 2 o 2 catalase gluthatione peroxidase gpx; reactions 6 and 7 and thioredoxin peroxidase trx; reaction 8 are preferentially distributed in cytosol and peroxisomes.
1516	CAT	catalase	catalase	1.0	considering the reduction to h 2 o by liver cytosolic gpx and catalase at the respective concentrations of 2.7 x 10 m and 1.2 x 10 m and the rate constants for reactions 7 and 8 the no dependent [h 2 o 2 ] ss could be calculated as follows 17 :
1516	CAT	catalase	catalase	1.0	lation of [h 2 o 2 ] ss implies an effective regulation of the different pathways participating in the process including the concentration and activities of mtnos cytosolic classic nos isoforms mnsod catalase and peroxidases.
1516	CAT	catalase	catalase	1.0	in this study cells were reverted to a normal phenotype by cotransfection with catalase and the authors concluded that a major role of h 2 o 2 is to activate genes related to the proliferating cascade.
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	ap 1	1.0	erks stimulate cell proliferation and induction of active cyclin d 1 by different mechanisms including the enhancement of ap 1 activity.
10436	RPS6KB1	ribosomal protein S6 kinase, 70kDa, polypeptide 1	p70 s6k	1.0	another mechanism is the activation of specific phosphorylation cascades that participate in the progression of the cell cycle; for instance h 2 o 2 acts as a messenger in growth factor induced p70 s6k signaling pathway in mouse epidermal cells which plays an important role in the transition from g 0 /g 1 to s phase of the cell cycle 9 .
2432	CSF1	colony stimulating factor 1 (macrophage)	macrophage colony stimulating factor	1.0	activation of a myeloid leukemia cell line tf 1a by granulocyte/macrophage colony stimulating factor induced only a transient activation of mek and erk1/2 and 50% increase in cell proliferation whereas prolonged stimulation with 10 to 10 m pma underwent 91 98% cell differentiation without proliferat
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	the proapoptotic effects depend on translocation of bax to mitochondria and generation of ros and ultimately on the release of cytochrome c but in a caspase independent manner.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	some antiapoptotic effects include s nitrosylation and inhibition of caspases increase of hsps and bcl 2 and activation of akt/pkb which induces cytoprotective gene expression through nf kappab activation 85 .
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	on the other hand proapoptotic effects of no include inhibition of nf kappab decreased bcl 2 expression 87 89 118 and increased p53 expression both by no mediated inhibition of proteasome degradation and by direct dna damage.
2874	NQO1	NAD(P)H dehydrogenase, quinone 1	nadh dehydrogenase	1.0	similar to the nadh dehydrogenase site of electron leak forming complex i being directed into the matrix side of the inner mitochondrial membrane in mitochondria o 2 can be detoxified by matrix antioxidant defense systems.
1516	CAT	catalase	catalase	1.0	isolated neonatal hepatocytes supplemented with h 2 o 2 catalase inhibitor 3 amino 1 2 4 triazole or l arginine invariably determined a dose dependent negative modulation of cell proliferation.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	caspases are cysteine proteases that cleave specific aspartate residues in other regulatory proteins like bcl 2 bax and mekk for review see ref 83 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	in the extrinsic pathway binding of membrane ligands like tnf alpha and fas to membrane receptors triggers the activation of caspases and the induction of apoptosis 6 106 .
576	APAF1	apoptotic peptidase activating factor 1	apoptotic protease activating factor 1	1.0	in the intrinsic program mitochondrial damage results in the release of cytochrome c triggering the assembly of the apoptosome complex with apoptotic protease activating factor 1 as central scaffold protein that directly recruits caspase 9 which in turn elicits caspase 3 effects 31 .
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	elease of cytochrome c triggering the assembly of the apoptosome complex with apoptotic protease activating factor 1 as central scaffold protein that directly recruits caspase 9 which in turn elicits caspase 3 effects 31 .
1511	CASP9	caspase 9, apoptosis-related cysteine peptidase	caspase 9	1.0	hondrial damage results in the release of cytochrome c triggering the assembly of the apoptosome complex with apoptotic protease activating factor 1 as central scaffold protein that directly recruits caspase 9 which in turn elicits caspase 3 effects 31 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	in the intrinsic program mitochondrial damage results in the release of cytochrome c triggering the assembly of the apoptosome complex with apoptotic protease activating factor 1 as central scaffold protein that directly recruits caspase 9 which in turn elicits caspase 3 effects 31 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	no can directly induce cytochrome c release through mitochondrial membrane potential loss 46 or by tyrosine nitration of cytochrome c 67 .
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	no donors or endogenous no induces apoptotic cell death with the activation of jnk/sapk and p38 mapk and caspase 3 or inactivation of nf kappab.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	disruption of the nf kappab gene is associated with embryo lethality; many antiapoptotic pathways like bcl 2 are induced by nf kappab.
992	BCL2L1	BCL2-like 1	bcl xl	1.0	no mediated p53 accumulation induces cell cycle arrest by p21 upregulation or apoptosis by increase in bax/bcl xl cytochrome c release and caspase activation 100 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	no mediated p53 accumulation induces cell cycle arrest by p21 upregulation or apoptosis by increase in bax/bcl xl cytochrome c release and caspase activation 100 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	on the other hand no has antiapoptotic effects that can be associated with cgmp production which suppresses mitochondrial cytochrome c release ceramide generation and caspase activation 46 77 .
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	other antiapoptotic no pathways include s nitrosylation and inactivation of caspases thiols and upregulation of antiapoptotic genes like that of heme oxygenase 127 and hsp70 which protects hepatocytes from apoptosis induced by oxidative and nitrative stress 46 .