The autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes.
The autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes.
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Cav-1的自噬降解导致PA诱导的星形胶质细胞凋亡和炎症
DOI：
10.1038/s41419-018-0795-3
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发表时间：
2018-07-10
影响因子：
9
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Chen Z;Nie SD;Qu ML;Zhou D;Wu LY;Shi XJ;Ma LR;Li X;Zhou SL;Wang S;Wu J
棕榈酸（PA）的积累与肥胖有关，可诱导星形胶质细胞的凋亡性细胞死亡和炎症。小窝蛋白-1（Cav-1）是星形胶质细胞生存的必需蛋白质，可以通过自噬降解，自噬是一把双刃剑，既可以促进细胞生存，也可以促进细胞死亡。本研究的目的是阐明Cav-1的自噬降解是否参与PA诱导的海马星形胶质细胞凋亡和炎症。本研究发现：（1）PA通过自噬诱导细胞凋亡和炎症反应;（2）Cav-1在PA诱导的自噬中降解，PA诱导的自噬不依赖Cav-1的降解;（3）Cav-1的降解参与PA诱导的自噬依赖的细胞凋亡和炎症反应;（4）慢性高脂饮食（HFD）诱导大鼠海马星形胶质细胞Cav-1降解、凋亡、自噬和炎症反应。我们的研究结果表明，Cav-1的自噬降解有助于PA诱导的星形胶质细胞凋亡和炎症。因此，Cav-1可能是PA蓄积引起的中枢神经系统损伤的潜在治疗靶点。
The accumulation of palmitic acid (PA), implicated in obesity, can induce apoptotic cell death and inflammation of astrocytes. Caveolin-1 (Cav-1), an essential protein for astrocytes survival, can be degraded by autophagy, which is a double-edge sword that can either promote cell survival or cell death. The aim of this study was to delineate whether the autophagic degradation of Cav-1 is involved in PA-induced apoptosis and inflammation in hippocampal astrocytes. In this study we found that: (1) PA caused apoptotic death and inflammation by autophagic induction; (2) Cav-1 was degraded by PA-induced autophagy and PA induced autophagy in a Cav-1-independent manner; (3) the degradation of Cav-1 was responsible for PA-induced autophagy-dependent apoptotic cell death and inflammation; (4) chronic high-fat diet (HFD) induced Cav-1 degradation, apoptosis, autophagy, and inflammation in the hippocampal astrocytes of rats. Our results suggest that the autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes. Therefore, Cav-1 may be a potential therapeutic target for central nervous system injuries caused by PA accumulation.
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