Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxic-ischemic encephalopathy (HIE) is a serious clinical problem, responsible for many cases of motor impairment, cognitive deficits, and mortality. Transient receptor potential canonical (TRPC) channels are nonselective cation channels that play a role in many disorders, including trauma, pulmonary hypertension, and excitotoxicity. However, the properties and underlying mechanisms of TRPC channels in HIE are still controversial. Extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) are central signaling pathways that transmit signals from extracellular to intracellular agents and mediate prosurvival, proliferation, and motility proteins. The relationship between TRPC channels, ERK, and mTOR is unclear. We used oxygen-glucose deprivation/reoxygenation in primary cortical neurons and PC12 cells to mimic an HIE episode. The potential effects and mechanisms of TRPC channels were examined. MNC (M: MK-801; N: nimodipine; C: CNQX) were used to exclude the interference of N-methyl-D-aspartate receptors, AMPK receptors, and calcium channels. We administered TRPC inhibitor SKF96365 to the cells, and then measured cell apoptosis and expression of ERK and mTOR signal pathways. At the same time, an ERK inhibitor or an mTOR agonist was used to further ensure the relation between TRPC channels and ERK, mTOR. Results showed that hypoxia-ischemia clearly induced cell apoptosis, activated the ERK pathway, and suppressed the mTOR pathway. Blocking of TRPC channels could enhance hypoxia-ischemia-induced apoptosis and lead to increased p-ERK pathway activity and decreased p-mTOR pathway activity. However, the ERK inhibitor or the mTOR agonist could reverse the effect of SKF96365. This study suggests that TRPC channels may be an effective treatment for HIE, regulating the ERK and mTOR pathways.
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PMID:Protective effects of transient receptor potential canonical channels on oxygen-glucose deprivation-induced cell injury in neurons and PC12 cells. 2753 78

Hypoxic-ischemic encephalopathy (HIE) is detrimental to newborns and is associated with high mortality and poor prognosis. Thus, the primary aim of the present study was to determine whether glycine could (1) attenuate HIE injury in rats and hypoxic stress in PC12 cells and (2) downregulate mitochondria-mediated autophagy dependent on the adenosine monophosphate- (AMP-) activated protein kinase (AMPK) pathway. Experiments conducted using an in vivo HIE animal model and in vitro hypoxic stress to PC12 cells revealed that intense autophagy associated with mitochondrial function occurred during in vivo HIE injury and in vitro hypoxic stress. However, glycine treatment effectively attenuated mitochondria-mediated autophagy. Additionally, after identifying alterations in proteins within the AMPK pathway in rats and PC12 cells following glycine treatment, cyclosporin A (CsA) and 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside (AICAR) were administered in these models and indicated that glycine protected against HIE and CoCl2 injury by downregulating mitochondria-mediated autophagy that was dependent on the AMPK pathway. Overall, glycine attenuated hypoxic-ischemic injury in neurons via reductions in mitochondria-mediated autophagy through the AMPK pathway both in vitro and in vivo.
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PMID:Glycine Protects against Hypoxic-Ischemic Brain Injury by Regulating Mitochondria-Mediated Autophagy via the AMPK Pathway. 3088 90