)| PMID |
17956327 ( ) |
|---|---|
| Title | Respiratory plasticity following intermittent hypoxia: roles of protein phosphatases and reactive oxygen species. |
| Abstract | Plasticity is an important property of the respiratory control system. One of the best-studied models of respiratory plasticity is pLTF (phrenic long-term facilitation). pLTF is a progressive increase in phrenic motor output lasting several hours following acute exposure to intermittent hypoxia. Similar to many other forms of neuroplasticity, pLTF is pattern-sensitive; it is induced by intermittent, but not sustained hypoxia of similar cumulative duration. Our understanding of the cellular/synaptic mechanisms underlying pLTF has increased considerably in recent years. Here, we review accumulating evidence suggesting that the pattern-sensitivity of pLTF arises substantially from differential reactive oxygen species formation and subsequent protein phosphatase inhibition during intermittent compared with sustained hypoxia in or near phrenic motor neurons. A detailed understanding of the cellular/synaptic mechanisms of pLTF may provide the rationale for new pharmacological approaches in the treatment of severe ventilatory control disorders, such as obstructive sleep apnoea and respiratory insufficiency either following spinal cord injury or during neurodegenerative diseases such as amyotrophic lateral sclerosis. Linden Drive, Madison, WI 53706, U.S.A. |
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 |
|---|---|---|---|---|
| 1033 | BDNF | brain-derived neurotrophic factor | 14 | brain derived neurotrophic factor | BDNF | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 7 | Akt | PKB | protein kinase b | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 7 | SOD | superoxide dismutase | |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | 5 | ERK | MAPKs | |
| 727 | ARTN | artemin | 3 | neurotrophic factor | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 3 | nadph oxidase | |
| 9391 | PRKAR2A | protein kinase, cAMP-dependent, regulatory, type II, alpha | 2 | protein kinase a | |
| 8032 | NTRK2 | neurotrophic tyrosine kinase, receptor, type 2 | 2 | TrkB | |
| 9393 | PRKCA | protein kinase C, alpha | 2 | protein kinase c | |
| 6879 | MAPK6 | mitogen-activated protein kinase 6 | 2 | extracellular signal regulated kinase | |
| 12805 | XDH | xanthine dehydrogenase | 1 | xanthine oxidase | |
| 4571 | GRIA1 | glutamate receptor, ionotropic, AMPA 1 | 1 | glutamate receptor | |
| 9308 | PPP2R4 | protein phosphatase 2A activator, regulatory subunit 4 | 1 | protein phosphatase 2a | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 4.2 | New synthesis and release of BDNF (brain-derived brain-derived neurotrophic factor is necessary and sufficient for pLTF |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 4.2 | AIH increases BDNF protein levels near phrenic motor neurons and this increase correlates |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 4.2 | The 5-HT-dependent increase in BDNF synthesis following AIH is necessary for pLTF expression since translational |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 4.2 | AIH is necessary for pLTF expression since translational inhibition of BDNF mRNA with siRNAs (small small interfering RNAs blocks both increased |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 4.2 | mRNA with siRNAs (small small interfering RNAs blocks both increased BDNF protein levels and pLTF receptor tyrosine kinase inhibitors also block |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 4.2 | BDNF is sufficient to elicit pLTF since localized application of BDNF |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 4.2 | BDNF is sufficient to elicit pLTF since localized application of BDNF protein near phrenic motor neurons elicits long-lasting phrenic motor facilitation |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 4.2 | (protein protein kinase C activation stimulating new protein synthesis including BDNF |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 4.2 | Released BDNF then activates its high-affinity receptor TrkB (tropomyosin tropomyosin receptor kinase |
| 8032 | NTRK2 | neurotrophic tyrosine kinase, receptor, type 2 | TrkB | 1.9 | Released BDNF then activates its high-affinity receptor TrkB (tropomyosin tropomyosin receptor kinase B resulting in the phosphorylation of |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK | 0.9 | (tropomyosin tropomyosin receptor kinase B resulting in the phosphorylation of ERK (extracellular-signal-regulated extracellular-signal-regulated kinase MAPKs (mitogen-activated mitogen-activated protein kinases and Akt |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPKs | 0.9 | B resulting in the phosphorylation of ERK (extracellular-signal-regulated extracellular-signal-regulated kinase MAPKs (mitogen-activated mitogen-activated protein kinases and Akt also called PKB (protein |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.8 | ERK (extracellular-signal-regulated extracellular-signal-regulated kinase MAPKs (mitogen-activated mitogen-activated protein kinases and Akt also called PKB (protein protein kinase B |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | PKB | 0.8 | kinase MAPKs (mitogen-activated mitogen-activated protein kinases and Akt also called PKB (protein protein kinase B |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK | 0.9 | phosphatases that may play a role in neural plasticity including ERK and the serine/threonine serine threonine protein phosphatases 1 2A and |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK | 0.9 | is necessary for pLTF 42 and activated forms of both ERK and PKB (Akt) Akt are increased in the ventral cervical |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | PKB | 0.8 | for pLTF 42 and activated forms of both ERK and PKB (Akt) Akt are increased in the ventral cervical spinal cord |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.8 | 42 and activated forms of both ERK and PKB (Akt) Akt are increased in the ventral cervical spinal cord following intermittent |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | SOD (superoxide superoxide dismutase prevent excessive ROS accumulation 46 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | AIH-induced pLTF also requires ROS since pre-treatment with a SOD mimetic abolishes pLTF 23 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | following AIH although changes in superoxide anion levels (e.g e.g SOD mimetic can disrupt levels of other ROS species such as |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | with okadaic acid restores pLTF in animals pre-treated with a SOD mimetic (P.M P.M MacFarlane and G.S Mitchell unpublished work but |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 4.2 | Key words brain-derived neurotrophic factor (BDNF), BDNF 5-hydroxytryptamine (5-HT), 5-HT long-term facilitation pattern-sensitivity phosphorylation plasticity |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 4.2 | Abbreviations used AIH acute intermittent hypoxia BDNF brain-derived neurotrophic factor ERK extracellular-signal-regulated kinase 5-HT 5-hydroxytryptamine LTF long-term |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK | 0.9 | Abbreviations used AIH acute intermittent hypoxia BDNF brain-derived neurotrophic factor ERK extracellular-signal-regulated kinase 5-HT 5-hydroxytryptamine LTF long-term facilitation pLTF phrenic LTF |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | PKB | 0.8 | LTF long-term facilitation pLTF phrenic LTF PKA protein kinase A PKB protein kinase B PKC protein kinase C ROS reactive oxygen |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | kinase B PKC protein kinase C ROS reactive oxygen species SOD superoxide dismutase TrkB tropomyosin receptor kinase B |
| 8032 | NTRK2 | neurotrophic tyrosine kinase, receptor, type 2 | TrkB | 1.9 | protein kinase C ROS reactive oxygen species SOD superoxide dismutase TrkB tropomyosin receptor kinase B |
| 727 | ARTN | artemin | neurotrophic factor | 1.0 | new synthesis and release of bdnf brain derived neurotrophic factor is necessary and sufficient for pltf in vivo [ 21 ]. |
| 1033 | BDNF | brain-derived neurotrophic factor | brain derived neurotrophic factor | 1.0 | new synthesis and release of bdnf brain derived neurotrophic factor is necessary and sufficient for pltf in vivo [ 21 ]. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | pkc protein kinase c activation] stimulating new protein synthesis including bdnf. |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | protein kinase b | 1.0 | igh affinity receptor trkb tropomyosin receptor kinase b resulting in the phosphorylation of erk extracellular signal regulated kinase mapks mitogen activated protein kinases and akt [also called pkb protein kinase b ]. |
| 6879 | MAPK6 | mitogen-activated protein kinase 6 | extracellular signal regulated kinase | 1.0 | released bdnf then activates its high affinity receptor trkb tropomyosin receptor kinase b resulting in the phosphorylation of erk extracellular signal regulated kinase mapks mitogen activated protein kinases and akt [also called pkb protein kinase b ]. |
| 4571 | GRIA1 | glutamate receptor, ionotropic, AMPA 1 | glutamate receptor | 1.0 | we postulate that these activated kinases phosphorylate glutamate receptors inducing glutamate receptor trafficking inserting more receptors in the post synaptic membrane and strengthening synapses between glutamatergic brainstem respiratory neurons and phrenic motor neurons. |
| 9391 | PRKAR2A | protein kinase, cAMP-dependent, regulatory, type II, alpha | protein kinase a | 1.0 | for example pka protein kinase a and pkc both modulate basal respiratory drive currents in medullary respiratory neurons including expiratory neurons in the caudal medulla [ 31 32 ] inspiratory neurons in the pre b_amp_#246;tzinger |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ros are continuously generated in cells through enzymatic e.g nadph oxidase and xanthine oxidase and non enzymatic e.g mitochondrial electron transport chain and receptor activation processes [ 46 ]. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | ros are continuously generated in cells through enzymatic e.g nadph oxidase and xanthine oxidase and non enzymatic e.g mitochondrial electron transport chain and receptor activation processes [ 46 ]. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | sod superoxide dismutase ] prevent excessive ros accumulation [ 46 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase may generate the ros necessary for pltf since apocynin an nadph oxidase and superoxide anion inhibitor blocks pltf [ 24 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | indeed putative phrenic motor neurons and nearby astrocytes express subunits of the nadph oxidase complex i satriotomo p.m macfarlane d.j harrigan and g.s mitchell unpublished work . |
| 9308 | PPP2R4 | protein phosphatase 2A activator, regulatory subunit 4 | protein phosphatase 2a | 1.0 | indeed in vitro application of h 2 o 2 to cervical spinal cord homogenates significantly inhibits the activity of the okadaic acid sensitive serine/threonine phosphatase protein phosphatase 2a j.e.r wilkerson and g.s mitchell unpublished work . |
| 727 | ARTN | artemin | neurotrophic factor | 1.0 | key words: brain derived neurotrophic factor bdnf 5 hydroxytryptamine 5 ht long term facilitation pattern sensitivity phosphorylation plasticity. |
| 1033 | BDNF | brain-derived neurotrophic factor | brain derived neurotrophic factor | 1.0 | key words: brain derived neurotrophic factor bdnf 5 hydroxytryptamine 5 ht long term facilitation pattern sensitivity phosphorylation plasticity. |
| 727 | ARTN | artemin | neurotrophic factor | 1.0 | abbreviations used: aih acute intermittent hypoxia; bdnf brain derived neurotrophic factor; erk extracellular signal regulated kinase; 5 ht 5 hydroxytryptamine; ltf long term facilitation; pltf phrenic ltf; pka protein kinase a; pkb protein kinase b; pkc protein kinase c; ros reactive oxyg |
| 9391 | PRKAR2A | protein kinase, cAMP-dependent, regulatory, type II, alpha | protein kinase a | 1.0 | ns used: aih acute intermittent hypoxia; bdnf brain derived neurotrophic factor; erk extracellular signal regulated kinase; 5 ht 5 hydroxytryptamine; ltf long term facilitation; pltf phrenic ltf; pka protein kinase a; pkb protein kinase b; pkc protein kinase c; ros reactive oxygen species; sod superoxide dismutase; trkb tropomyosin receptor kinase b. |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | protein kinase b | 1.0 | ermittent hypoxia; bdnf brain derived neurotrophic factor; erk extracellular signal regulated kinase; 5 ht 5 hydroxytryptamine; ltf long term facilitation; pltf phrenic ltf; pka protein kinase a; pkb protein kinase b; pkc protein kinase c; ros reactive oxygen species; sod superoxide dismutase; trkb tropomyosin receptor kinase b. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | f brain derived neurotrophic factor; erk extracellular signal regulated kinase; 5 ht 5 hydroxytryptamine; ltf long term facilitation; pltf phrenic ltf; pka protein kinase a; pkb protein kinase b; pkc protein kinase c; ros reactive oxygen species; sod superoxide dismutase; trkb tropomyosin receptor kinase b. |
| 6879 | MAPK6 | mitogen-activated protein kinase 6 | extracellular signal regulated kinase | 1.0 | abbreviations used: aih acute intermittent hypoxia; bdnf brain derived neurotrophic factor; erk extracellular signal regulated kinase; 5 ht 5 hydroxytryptamine; ltf long term facilitation; pltf phrenic ltf; pka protein kinase a; pkb protein kinase b; pkc protein kinase c; ros reactive oxygen species; sod superoxide dismutase; trkb |
| 1033 | BDNF | brain-derived neurotrophic factor | brain derived neurotrophic factor | 1.0 | abbreviations used: aih acute intermittent hypoxia; bdnf brain derived neurotrophic factor; erk extracellular signal regulated kinase; 5 ht 5 hydroxytryptamine; ltf long term facilitation; pltf phrenic ltf; pka protein kinase a; pkb protein kinase b; pkc protein kinase c; ros reactive oxyg |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | lar signal regulated kinase; 5 ht 5 hydroxytryptamine; ltf long term facilitation; pltf phrenic ltf; pka protein kinase a; pkb protein kinase b; pkc protein kinase c; ros reactive oxygen species; sod superoxide dismutase; trkb tropomyosin receptor kinase b. |