Abstract
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.
Highlights
In the central nervous system (CNS), lipids are majorly synthesized and metabolized by astrocytes[1,2]
It has been demonstrated that rat hippocampal astrocytes are more sensitive to oxygenglucose deprivation (OGD) than cortical astrocytes[32], suggesting that sensitivity of astrocytes on harmful stimuli might be dependent on the heterogeneity of astrocytes in different regions[33]
When the level of autophagy rises to certain extent, some functional proteins such as Cav-1 26, catalase[13], and dBruce[14] were degraded, leading to apoptosis[26], which could be inhibited by preventing the destructive degradation of these functional proteins[15]
Summary
In the central nervous system (CNS), lipids are majorly synthesized and metabolized by astrocytes[1,2]. In order to provide an effective intervention for lipotoxicity of PA in CNS, further investigation is required to more precisely delineate the molecular mechanisms by which PA causes cellular damage to astrocytes. A conserved evolutionary process in all eukaryotic cells, is responsible for the sequestration and delivery of damaged organelles and macromolecule into lysosomes for degradation, which acts as a pro-survival mechanism[9,10,11,12]. It has been reported that autophagy aggravated the lipotoxicity of PA in endothelial cells[16] and cardiomyocytes[17], whereas reversed the damage caused by PA in human gastric cancer cells[18] and adipocytes[19], suggesting that the contribution of autophagy to cell fates, survival or death, varied in a cell typedependent fashion. We focus on the role of autophagy in PA-caused lipotoxicity in astrocytes
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