Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro.
Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro.
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DOI：
10.1038/srep42764
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发表时间：
2017-02-22
影响因子：
4.6
通讯作者：
Du XG
中科院分区：
文献类型：
--
作者：
Jiang XS;Chen XM;Wan JM;Gui HB;Ruan XZ;Du XG
自噬是一种高度保守的降解过程，参与蛋白质和受损细胞器的清除，以维持细胞内稳态和细胞完整性。2型糖尿病通常伴有血脂异常和游离脂肪酸（FFAs）水平升高。足细胞作为滤过屏障的重要组成部分，易受脂质紊乱的影响。足细胞的丢失导致蛋白尿，这参与了糖尿病肾病的发病机制。在本研究中，我们证明棕榈酸（PA）促进足细胞的自噬。我们进一步发现，PA增加了足细胞中活性氧（ROS）的产生，NAC（N-乙酰半胱氨酸），一种有效的抗氧化剂，显着消除过量的ROS和抑制自噬，表明ROS的产生增加与棕榈酸诱导的足细胞自噬有关。此外，我们还发现，PA刺激降低足细胞线粒体膜电位，诱导足细胞凋亡，而氯喹（CQ）抑制自噬增强棕榈酸诱导的细胞凋亡伴随着增加的ROS产生，和雷帕霉素（Rap）刺激自噬显着抑制棕榈酸诱导的ROS产生和细胞凋亡。总之，这些体外研究结果表明，PA诱导的足细胞自噬是由ROS产生介导的，自噬对PA诱导的足细胞凋亡起保护作用。
Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes. We further found that PA increased the production of reactive oxygen species (ROS) in podocytes and that NAC (N-acetyl-cysteine), a potent antioxidant, significantly eliminated the excessive ROS and suppressed autophagy, indicating that the increased generation of ROS was associated with the palmitic acid-induced autophagy in podocytes. Moreover, we also found that PA stimulation decreased the mitochondrial membrane potential in podocytes and induced podocyte apoptosis, while the inhibition of autophagy by chloroquine (CQ) enhanced palmitic acid-induced apoptosis accompanied by increased ROS generation, and the stimulation of autophagy by rapamycin (Rap) remarkably suppressed palmitic acid-induced ROS generation and apoptosis. Taken together, these in vitro findings suggest that PA-induced autophagy in podocytes is mediated by ROS production and that autophagy plays a protective role against PA-induced podocyte apoptosis.