)| PMID |
16978905 ( ) |
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| Title | Free radicals and antioxidants in normal physiological functions and human disease. |
| Abstract | Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric oxide, NO(*)) are well recognised for playing a dual role as both deleterious and beneficial species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. Overproduction of ROS (arising either from mitochondrial electron-transport chain or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA. In contrast, beneficial effects of ROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate concentrations and involve physiological roles in cellular responses to noxia, as for example in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. Ironically, various ROS-mediated actions in fact protect cells against ROS-induced oxidative stress and re-establish or maintain "redox balance" termed also "redox homeostasis". The "two-faced" character of ROS is clearly substantiated. For example, a growing body of evidence shows that ROS within cells act as secondary messengers in intracellular signalling cascades which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS and sources of free radical generation; (ii) damage to DNA, to proteins, and to lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the maintenance of cellular "redox homeostasis"; (iv) overview of ROS-induced signaling pathways; (v) role of ROS in redox regulation of normal physiological functions, as well as (vi) role of ROS in pathophysiological implications of altered redox regulation (human diseases and ageing). Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury. SK-812 37 Bratislava, Slovakia. marian.valko@stuba.sk |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 12805 | XDH | xanthine dehydrogenase | 13 | xanthine oxidoreductase | xanthine oxidase | xanthine dehydrogenase | XOR | |
| 117 | ACO1 | aconitase 1, soluble | 4 | IRE-BP | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 4 | SOD | superoxide dismutase | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 2 | p67 phox | |
| 118 | ACO2 | aconitase 2, mitochondrial | 2 | aconitase | |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | 2 | p40 | MAPK | |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 2 | endothelial nitric oxide synthase | eNOS | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 2 | IL-6 | il 6 | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 2 | angiotensin ii | ang ii | |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 2 | NOS | NOSs | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 2 | p22 phox | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 1 | gp91 phox | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 1 | Rac | |
| 11740 | TF | transferrin | 1 | transferrin | |
| 4623 | GSR | glutathione reductase | 1 | glutathione reductase | |
| 9855 | RAP1A | RAP1A, member of RAS oncogene family | 1 | Rap1A | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 1 | TNF-A | |
| 25806 | GSTCD | glutathione S-transferase, C-terminal domain containing | 1 | glutathione s transferase | |
| 1516 | CAT | catalase | 1 | catalase | |
| 4626 | GSTA1 | glutathione S-transferase A1 | 1 | GST | |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | 1 | ho 2 | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 1 | p47 | |
| 4886 | HFE | hemochromatosis | 1 | hemochromatosis | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | generated by tightly regulated enzymes such as NO synthase (NOS) NOS and NAD(P)H NAD P H oxidase isoforms respectively |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | when McCord and Fridovich discovered the enzyme superoxide dismutase (SOD) SOD and thus provided convincing evidence about the importance of free |
| 117 | ACO1 | aconitase 1, soluble | IRE-BP | 0.6 | contains also iron responsive elements (IRE)-binding IRE -binding protein (IRE-BP) IRE-BP |
| 117 | ACO1 | aconitase 1, soluble | IRE-BP | 0.6 | intracellular iron levels and accordingly modifies the ability of the IRE-BP to interact with iron-responsive elements (IREs) IREs |
| 117 | ACO1 | aconitase 1, soluble | IRE-BP | 0.6 | IRE-BP produced in iron-replete cells has aconitase activity ( Han et |
| 118 | ACO2 | aconitase 2, mitochondrial | aconitase | 1.3 | IRE-BP produced in iron-replete cells has aconitase activity ( Han et al. 2005 |
| 118 | ACO2 | aconitase 2, mitochondrial | aconitase | 1.3 | In mammalian cells oxidants are able to convert cytosolic aconitase into active IRE-BP which increases the _amp_#x201c free iron_amp_#x201d concentration |
| 117 | ACO1 | aconitase 1, soluble | IRE-BP | 0.6 | cells oxidants are able to convert cytosolic aconitase into active IRE-BP which increases the _amp_#x201c free iron_amp_#x201d concentration intracellularly both by |
| 12805 | XDH | xanthine dehydrogenase | XOR | 2.1 | forms of the same enzyme known as xanthine oxidoreductase (XOR) XOR ( Borges Fernandes _amp_#x26 Roleira 2002 Vorbach Harrison _amp_#x26 Capecchi |
| 12805 | XDH | xanthine dehydrogenase | XOR | 2.1 | In purine catabolism XOR catalyzes the oxidative hydroxylation of hypoxanthine to xanthine and subsequently |
| 12805 | XDH | xanthine dehydrogenase | XOR | 2.1 | XOR has therefore important functions as a cellular defense enzyme against |
| 12805 | XDH | xanthine dehydrogenase | XOR | 2.1 | acid and numerous free radicals (ROS ROS and RNS makes XOR an important protective regulator of the cellular redox potential |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 0.0 | enzyme complex consists of two membrane-bound components gp91 phox and p22 phox which comprise cytochrome b558 the enzymatic centre of the |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.3 | After activation cytosolic components involving p47 phox p67 phox p40 phox and the small G coupled |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 | 0.3 | After activation cytosolic components involving p47 phox p67 phox p40 phox and the small G coupled proteins Rac |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p40 | 0.5 | After activation cytosolic components involving p47 phox p67 phox p40 phox and the small G coupled proteins Rac and Rap1A |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Rac | 0.3 | p67 phox p40 phox and the small G coupled proteins Rac and Rap1A translocate to the membrane to form the active |
| 9855 | RAP1A | RAP1A, member of RAS oncogene family | Rap1A | 0.6 | p40 phox and the small G coupled proteins Rac and Rap1A translocate to the membrane to form the active enzyme complex |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOSs | 1.2 | generated in biological tissues by specific nitric oxide synthases (NOSs), NOSs which metabolise arginine to citrulline with the formation of NO |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | 2 Superoxide radical is dismutated by the superoxide dismutase (SOD) SOD to hydrogen peroxide |
| 4626 | GSTA1 | glutathione S-transferase A1 | GST | 0.3 | 17 4-hydroxynonenal is rendered into an innocuous glutathiyl adduct (GST, GST glutathione S -transferase |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 0.5 | Fig 2._amp_#xa0 ROS-induced MAPK signalling pathways |
| 12805 | XDH | xanthine dehydrogenase | XOR | 2.1 | (B) B The xanthine-oxidoreductase (XOR) XOR system |
| 12805 | XDH | xanthine dehydrogenase | XOR | 2.1 | XOR exists in two enzymatic forms as a XD (xanthine xanthine |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | The endothelial nitric oxide synthase (eNOS) eNOS with the deficiency of cofactors l -arginine and BH 4 |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.0 | variety of vasoactive (Angiotensin Angiotensin II Ang II inflammatory (IL-6, IL-6 TNF-_amp_#x3b1 and growth (TGF-_amp_#x3b2;) TGF-_amp_#x3b2 factors |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 0.3 | of vasoactive (Angiotensin Angiotensin II Ang II inflammatory (IL-6, IL-6 TNF-_amp_#x3b1 and growth (TGF-_amp_#x3b2;) TGF-_amp_#x3b2 factors |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | a second epoch of the research of free radicals in biological systems was explored in 1969 when mccord and fridovich discovered the enzyme superoxide dismutase sod and thus provided convincing evidence about the importance of free radicals in living systems mccord _amp_#x26; fridovich 1969 . |
| 11740 | TF | transferrin | transferrin | 1.0 | tosolic aconitase into active ire bp which increases the _amp_#x201c;free iron_amp_#x201d; concentration intracellularly both by decreasing the biosynthesis of ferritin and increasing biosynthesis of transferrin receptors. |
| 4886 | HFE | hemochromatosis | hemochromatosis | 1.0 | however organisms overloaded by iron as in the conditions of hemochromatosis b thalassemia hemodialysis contain higher amounts of _amp_#x201c;free available iron_amp_#x201d; and this can have deleterious effects. _amp_#x201c;free iron_amp_#x201d; is transported into an interm |
| 12805 | XDH | xanthine dehydrogenase | xanthine dehydrogenase | 1.0 | the looh dependent pathway of ho 2 initiated fatty acid peroxidation may be relevant to mechanisms of lipid peroxidation initiation in vivo .xanthine oxidase xo ec 1.1.3.22 and xanthine dehydrogenase xd ec 1.1.1.204 are interconvertible forms of the same enzyme known as xanthine oxidoreductase xor borges fernandes _amp_#x26; roleira 2002 ; vorbach harrison _amp_#x26; capecchi 2003 . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | the looh dependent pathway of ho 2 initiated fatty acid peroxidation may be relevant to mechanisms of lipid peroxidation initiation in vivo .xanthine oxidase xo ec 1.1.3.22 and xanthine dehydrogenase xd ec 1.1.1.204 are interconvertible forms of the same enzyme known as xanthine oxidoreductase xor borges fernandes _amp_#x26; roleira 2002 ; vorbach harriso |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidoreductase | 1.0 | y be relevant to mechanisms of lipid peroxidation initiation in vivo .xanthine oxidase xo ec 1.1.3.22 and xanthine dehydrogenase xd ec 1.1.1.204 are interconvertible forms of the same enzyme known as xanthine oxidoreductase xor borges fernandes _amp_#x26; roleira 2002 ; vorbach harrison _amp_#x26; capecchi 2003 . |
| 5014 | HMOX2 | heme oxygenase (decycling) 2 | ho 2 | 1.0 | the looh dependent pathway of ho 2 initiated fatty acid peroxidation may be relevant to mechanisms of lipid peroxidation initiation in vivo .xanthine oxidase xo ec 1.1.3.22 and xanthine dehydrogenase xd ec 1.1.1.204 are interconvertib |
| 1516 | CAT | catalase | catalase | 1.0 | the organelle also contains catalase which decomposes hydrogen peroxide and presumably prevents accumulation of this toxic compound. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | the enzyme complex consists of two membrane bound components gp91 phox and p22 phox which comprise cytochrome b558 the enzymatic centre of the complex. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | the enzyme complex consists of two membrane bound components gp91 phox and p22 phox which comprise cytochrome b558 the enzymatic centre of the complex. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | after activation cytosolic components involving p47 phox p67 phox p40 phox and the small g coupled proteins rac and rap1a translocate to the membrane to form the active enzyme complex. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | reaction 1: the superoxide anion radical is formed by the process of reduction of molecular oxygen mediated by nad p h oxidases and xanthine oxidase or non enzymatically by redox reactive compounds such as the semi ubiquinone compound of the mitochondrial electron transport chain. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | reaction 2: superoxide radical is dismutated by the superoxide dismutase sod to hydrogen peroxide. |
| 4623 | GSR | glutathione reductase | glutathione reductase | 1.0 | reaction 4: the oxidised glutathione gssg is reduced back to gsh by the enzyme glutathione reductase gred which uses nadph as the electron donor. |
| 25806 | GSTCD | glutathione S-transferase, C-terminal domain containing | glutathione s transferase | 1.0 | reaction 17: 4 hydroxynonenal is rendered into an innocuous glutathiyl adduct gst glutathione s transferase . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidoreductase | 1.0 | b the xanthine oxidoreductase xor system. |
| 12805 | XDH | xanthine dehydrogenase | xanthine dehydrogenase | 1.0 | xor exists in two enzymatic forms as a xd xanthine dehydrogenase and as an xo xanthine oxidase . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | xor exists in two enzymatic forms as a xd xanthine dehydrogenase and as an xo xanthine oxidase . |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | endothelial nitric oxide synthase | 1.0 | the endothelial nitric oxide synthase enos with the deficiency of cofactors l arginine and bh 4 6 r 5 6 7 8 tetrahydrobiopterin switches from a coupled state generating nitric oxide no to an uncoupled oxide generating superoxide o 2 _amp |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | the enzyme complex is activated in response to a variety of vasoactive angiotensin ii ang ii inflammatory il 6 tnf _amp_#x3b1; and growth tgf _amp_#x3b2; factors. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | the enzyme complex is activated in response to a variety of vasoactive angiotensin ii ang ii inflammatory il 6 tnf _amp_#x3b1; and growth tgf _amp_#x3b2; factors. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | the enzyme complex is activated in response to a variety of vasoactive angiotensin ii ang ii inflammatory il 6 tnf _amp_#x3b1; and growth tgf _amp_#x3b2; factors. |