Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, No 17 Qinghua East Road, Haidian District, Beijing, 100083, China.
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, No 17 Qinghua East Road, Haidian District, Beijing, 100083, China.
Food Chem Toxicol. 2019 Jan;123:268-274. doi: 10.1016/j.fct.2018.11.011. Epub 2018 Nov 5.
Induction of programmed cell death, mainly apoptosis (lipoapoptosis) is a major cellular consequence of the lipotoxicity, a harmful effect resulting from the overload of lipids. Both Endoplasmic reticulum (ER) stress and autophagy have been suggested to play important role in the regulation of lipoapoptosis. However, the exact mechanisms underlying lipoapoptosis remain unclear. In the present study, we aimed to investigate the functional role of Bax/Bak in lipoapoptosis using mouse embryonic fibroblasts (MEFs) cell culture model. Results showed that palmitate induced caspase-dependent apoptosis in wild-type Bax/Bak MEF cells, whereas a caspase-independent cell death was induced by palmitate in Bax/Bak knockout MEF cells, suggesting requirement of Bax/Bak in palmitate-induced caspase activation. More importantly, we found that the status of Bax/Bak is a determinant that governs the decision between the pro-survival or pro-death function of autophagy in response to palmitate exposure, and Bax/Bak is required for palmitate-induced activation of endoplasmic reticulum (ER) stress and subsequently ER stress-mediated apoptosis. The findings of the present study provided novel insights into understanding the mechanisms involved in the regulation of palmitate-induced lipoapoptosis.
诱导细胞程序性死亡，主要是细胞凋亡（脂肪细胞凋亡），是脂毒性的主要细胞后果，脂毒性是由脂质过载引起的有害作用。内质网（ER）应激和自噬被认为在调节脂肪细胞凋亡中发挥重要作用。然而，脂肪细胞凋亡的确切机制尚不清楚。在本研究中，我们旨在使用鼠胚胎成纤维细胞（MEF）细胞培养模型研究 Bax/Bak 在脂肪细胞凋亡中的功能作用。结果表明，软脂酸诱导野生型 Bax/Bak MEF 细胞中 caspase 依赖性细胞凋亡，而 Bax/Bak 敲除 MEF 细胞中软脂酸诱导 caspase 非依赖性细胞死亡，表明 Bax/Bak 在软脂酸诱导的 caspase 激活中是必需的。更重要的是，我们发现 Bax/Bak 的状态是决定自噬在应对软脂酸暴露时是发挥促生存还是促死亡功能的决定因素，并且 Bax/Bak 是软脂酸诱导的内质网（ER）应激和随后 ER 应激介导的细胞凋亡所必需的。本研究的结果为理解调节软脂酸诱导的脂肪细胞凋亡的机制提供了新的见解。
