自噬与p62/SQSTM1在肝缺血再灌注中的作用

Roles of autophagy and p62/SQSTMlin hepatic ischemia-reperfusion

自噬是溶酶体依赖性的降解系统,p62作为重要的蛋白载体,可促进受损蛋白经蛋白酶体和自噬体清除。p62在线粒体自噬等选择性自噬中发挥重要作用。p62与Keap1结合并通过自噬清除Keap1,这导致游离的Nrf2水平增加,而Nrf2又可促进p62表达。因此自噬、p62、Nrf2三者间存在密切的联系,相互调控。同时,Nrf2还可促进谷胱甘肽(Glutathione,GSH)和硫氧还蛋白(Thioredoxin,TXN)等多种分子的表达,而在肝缺血再灌注损伤过程中,肝细胞内这些分子可能参与细胞死亡的过程。因此,自噬与p62在肝缺血再灌注中的具体机制仍需进一步研究明确。

Autophagy is a lysosomal dependent degradation system,and p62 itself is an important protein carrier to facilitate the removal of damaged proteins by proteasomes and autophagosomes.p62 plays an important role in selective autophagy such as mitochondrial autophagy.p62 binds to Keap1 and clears Keap1 through autophagy,leading to increased levels of free Nrf2.Nrf2 can promote the expression of p62,glutathione(GSH)and thioredoxin(TXN).Therefore,autophagy,p62 and Nrf2 are closely related and mutually regulated.However,in the process of hepatic ischemia-reperfusion injury,these molecules in hepatocytes may participate in the process of cell death,and the specific mechanism still needs to be further studied.