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AMP 激活的蛋白激酶:对缺血性疾病的影响。

AMP-activated protein kinase: implications on ischemic diseases.

机构信息

Vascular Medicine Research Unit, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, MA 02139, USA.

出版信息

BMB Rep. 2012 Sep;45(9):489-95. doi: 10.5483/bmbrep.2012.45.9.169.

Abstract

Ischemia is a blockage of blood supply due to an embolism or a hemorrhage in a blood vessel. When an organ cannot receive oxygenated blood and can therefore no longer replenish its blood supply due to ischemia, stresses, such as the disruption of blood glucose homeostasis, hypoglycemia and hypoxia, activate the AMPK complex. LKB1 and CaMKKβ are essential activators of the AMPK signaling pathway. AMPK triggers proangiogenic effects through the eNOS protein in tissues with ischemic conditions, where cells are vulnerable to apoptosis, autophagy and necrosis. The AMPK complex acts to restore blood glucose levels and ATP levels back to homeostasis. This review will discuss AMPK, as well as its key activators (LKB1 and CaMKKβ), as a central energy regulator and evaluate the upstream and downstream regulating pathways of AMPK. We will also discuss how we can control this important enzyme in ischemic conditions to prevent harmful effects in patients with vascular damage.

摘要

缺血是由于血管中的栓塞或出血导致的血液供应阻塞。当一个器官由于缺血而无法接收含氧血液,并且因此无法再补充血液供应时,应激因素,如血糖稳态的破坏、低血糖和缺氧,会激活 AMPK 复合物。LKB1 和 CaMKKβ 是 AMPK 信号通路的必需激活剂。在缺血条件下,AMPK 通过组织中的 eNOS 蛋白触发促血管生成作用,其中细胞容易发生细胞凋亡、自噬和坏死。AMPK 复合物的作用是将血糖水平和 ATP 水平恢复到体内平衡。本综述将讨论 AMPK 及其关键激活剂(LKB1 和 CaMKKβ)作为中央能量调节剂,并评估 AMPK 的上游和下游调节途径。我们还将讨论如何在缺血条件下控制这种重要的酶,以防止血管损伤患者的有害影响。

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