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AMP-activated protein kinase is involved in induction of protective autophagy in astrocytes exposed to oxygen-glucose deprivation

机译:AMP激活的蛋白激酶参与暴露于缺氧-葡萄糖剥夺的星形胶质细胞中保护性自噬的诱导

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摘要

AMP-activated kinase (AMPK) acts as the intracellular ATP depletion sensor, which detects and limits increases in the AMP/ ATP ratio. AMPK may be significantly activated under stress conditions that deplete cellular ATP levels such as ischemia/ hypoxia or glucose deprivation. Recent studies strongly suggest that AMPK participates in autophagy regulation, but it is not known whether AMPK activated by ischemia regulates autophagy in astrocytes and the consequence of autophagy activation in ischemic astrocytes are unclear. We have investigated the contribution of AMPK to autophagy activation in rat primary astrocyte cultures subjected to ischemia-simulating conditions (combined oxygen glucose deprivation, OGD) and its potential effects on astrocyte damage induced by OGD (1-12 h). The evidence supports the conclusion that AMPK activation at early stages of OGD is involved in induction of protective autophagy in astrocytes. Inhibition of AMPK, either by siAMPKalpha1 or by compound C, significantly attenuated the expression of autophagy-related proteins and decrease of astrocyte viability following OGD. The findings provide additional data about the role of AMPK in ischemic astrocytes and downstream responses that may be involved in OGD-induced protective autophagy.
机译:AMP激活激酶(AMPK)充当细胞内ATP消耗传感器,可检测并限制AMP / ATP比率的增加。 AMPK在耗尽细胞ATP水平的应激条件(例如缺血/缺氧或葡萄糖缺乏)下会被显着激活。最近的研究强烈提示AMPK参与自噬调节,但尚不清楚缺血激活的AMPK是否调节星形胶质细胞的自噬,尚不清楚缺血性星形胶质细胞自噬活化的结果。我们已经研究了AMPK对大鼠缺血模拟条件下原代星形胶质细胞培养(结合氧葡萄糖剥夺,OGD)自噬激活的贡献及其对OGD诱导的星形胶质细胞损伤(1-12小时)的潜在影响。证据支持以下结论:OGD早期的AMPK激活与星形胶质细胞中保护性自噬的诱导有关。 siAMPKalpha1或化合物C对AMPK的抑制作用大大减弱了OGD后自噬相关蛋白的表达并降低了星形胶质细胞的生存能力。这些发现提供了有关AMPK在缺血性星形胶质细胞中的作用以及可能与OGD诱导的保护性自噬有关的下游反应的其他数据。

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