Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.27 (AMPK)
 6,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endoplasmic reticulum (ER) stress has been identified as a primary factor involved in brain ischemia-reperfusion injury progression. p21-activated kinase 2 (Pak2) is a novel ER function regulator. The aim of our study is to explore the influence of Pak2 on ER stress and determine whether melatonin attenuates ER stress-mediated cell death by modulating Pak2 expression in vitro using N2a cells. The results of our study demonstrated that hypoxia-reoxygenation (HR) injury repressed the levels of Pak2, an effect that was accompanied by activation of ER stress. In addition, decreased Pak2 was associated with oxidative stress, calcium overload, and caspase-12-mediated apoptosis activation in HR-treated N2a cells. Interestingly, melatonin treatment reversed the decreased Pak2 expression under HR stress. Knockdown of Pak2 abolished the protective effects of melatonin on ER stress, oxidative stress, and caspase-12-related N2a cells death. Additionally, we found that Pak2 was regulated by melatonin via the AMPK pathway; inhibition of AMPK prevented melatonin-mediated Pak2 upregulation, a result that was accompanied by an increase in N2a cell death. Altogether, these results identify the AMPK-Pak2 axis as a new signaling pathway responsible for ER stress and N2a cell viability under HR injury. Modulation of the AMPK-Pak2 cascade via supplementation of melatonin might be considered an effective approach to attenuate reperfusion-mediated N2a cell damage via repression of ER stress.
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PMID:Melatonin ameliorates endoplasmic reticulum stress in N2a neuroblastoma cell hypoxia-reoxygenation injury by activating the AMPK-Pak2 pathway. 3097 81

Cardiac reperfusion injury has been found to be associated with endoplasmic reticulum (ER) stress. Recently, p21-activated kinase 2 (Pak2) has been identified as a primary mediator of ER stress in chronic myocardial injury. Melatonin, a biological clock-related hormone, has been demonstrated to attenuate heart reperfusion burden by modulating ER stress and mitochondrial function. The aim of our study was to explore whether reperfusion-induced ER stress is modulated by melatonin through Pak2. Hypoxia reoxygenation (HR) was used in vitro to mimic reperfusion injury in cardiomyocytes. ER stress, oxidative stress, calcium overload, and cell death were measured through Western blotting, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and immunofluorescence with the assistance of siRNA transfection and pathway blocker treatment. The results of our study demonstrated that HR decreased the levels of Pak2 in cardiomyocytes in vitro, and inactivation of Pak2 was associated with ER stress, oxidative stress, calcium overload, caspase-12 activation, and cardiomyocytes apoptosis in vitro. Interestingly, melatonin treatment attenuated HR-mediated ER stress, redox imbalance, calcium overload, and caspase-12-related cardiomyocytes apoptosis, and these protective effects were dependent on Pak2 upregulation. Knockdown of Pak2 abolished the beneficial actions exerted by melatonin on HR-treated cardiomyocytes in vitro. Finally, we found that melatonin reversed Pak2 expression by activating the AMPK pathway and blockade of the AMPK pathway suppressed Pak2 upregulation and cardiomyocytes survival induced by melatonin in the presence of HR stress. Overall, our study reports that the AMPK-Pak2 axis, a novel signaling pathway modulated by melatonin, sends prosurvival signals for cardiomyocytes reperfusion injury through attenuation of ER stress in vitro.
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PMID:Melatonin-Mediated Pak2 Activation Reduces Cardiomyocyte Death Through Suppressing Hypoxia Reoxygenation Injury-Induced Endoplasmic Reticulum Stress. 3127 39