Acetyl-CoA carboxylase 2 suppression rescues human proximal tubular cells from palmitic acid induced lipotoxicity via autophagy
Acetyl-CoA carboxylase 2 suppression rescues human proximal tubular cells from palmitic acid induced lipotoxicity via autophagy
复制标题
乙酰辅酶 A 羧化酶 2 抑制可通过自噬将人近端肾小管细胞从棕榈酸诱导的脂毒性中拯救出来。
DOI：
10.1016/j.bbrc.2015.05.070
复制
发表时间：
2015-07-31
影响因子：
3.1
通讯作者：
Wan, Qiang
中科院分区：
文献类型：
--
作者：
Xin, Wei;Zhao, Xu;Wan, Qiang
自噬是哺乳动物细胞中降解受损蛋白质和细胞器的分解代谢过程。乙酰辅酶A羧化酶2（acetyl-CoA carboxylase 2，ACC 2）在脂肪酸代谢中起着重要作用，但ACC 2是否与自噬活性相关尚不清楚。本工作旨在研究ACC 2对棕榈酸（PA）诱导的人近端肾小管细胞脂毒性的影响以及自噬在此过程中的作用。在这里，我们表明，自噬诱导PA在HK-2细胞。此外，PA诱导的自噬受ACC 2抑制和CPTI抑制剂治疗的调节，这代表了改变的脂肪酸β-氧化。ACC 2的敲低减少了PA诱导的自噬，从而保护细胞免受PA诱导的脂毒性，减少脂质积累并拯救细胞活力。总之，本研究提出了PA诱导的肾脏脂毒性的一种新的自噬机制，并通过调节脂质β-氧化为糖尿病肾病提供了潜在的治疗策略。(C)2015 Elsevier Inc. All rights reserved.
Autophagy is a catabolic process that degrades damaged proteins and organelles in mammalian cells. Although acetyl-CoA carboxylase 2 (ACC2) plays a crucial role in the fatty acid metabolism, it keeps unknown whether ACC2 is associated with autophagic activity. The present work was designed to investigate the effects of ACC2 on palmitic acid (PA) induced lipotoxicity in human proximal tubular cells and the putative role of autophagy in this process. Here we show that autophagy was induced by PA in HK-2 cells. Moreover, the PA induced autophagy was regulated both by ACC2 suppression and CPTI inhibitor treatment, which represent an altered fatty acid beta-oxidation. And the knockdown of ACC2 reduced PA-induced autophagy and thus protects the cells from PA-induced lipotoxicity with attenuated lipid accumulation and rescued cell viability. Collectively, the present study proposed a novel autophagy-involved mechanism of PA-induced renal lipotoxicity and provided potential therapeutic strategy by modulating lipid beta-oxidation for diabetic nephropathy. (C) 2015 Elsevier Inc. All rights reserved.