Rotenone induces reductive stress and triacylglycerol deposition in C2C12 cells.
Rotenone induces reductive stress and triacylglycerol deposition in C2C12 cells.
复制标题
DOI：
10.1016/j.biocel.2013.09.011
复制
发表时间：
2013-12
影响因子：
4
通讯作者：
Han, Xianlin
中科院分区：
文献类型：
--
作者：
He, Quan;Wang, Miao;Petucci, Christopher;Gardell, Stephen J.;Han, Xianlin
环境鱼藤酮与帕金森病有关，因为它对线粒体呼吸链的复合体I具有抑制作用。虽然环境污染被认为是肥胖症发病率增加的原因之一，但鱼藤酮在肥胖症发病机制中的作用尚未被研究。我们以肌源性细胞C2C12为模型，用鸟枪式脂质组学作为脂质分析的工具，发现鱼藤酮处理导致细胞内三酰甘油(TAG)以时间和剂量依赖的方式深刻沉积。Tag的沉积是由于络合物I的抑制所致。进一步的研究表明，鱼藤酮诱导的线粒体应激包括降低线粒体耗氧速率、增加NADH/NAD+比值(即还原应激)和线粒体代谢产物。我们证明鱼藤酮激活了脂肪酸从头合成和标签合成，最终导致细胞内标签沉积。这些研究表明，线粒体压力增加可能是导致肥胖患者标签堆积的潜在机制。
Environmental rotenone is associated with Parkinson’s disease due to its inhibitory property to the complex I of mitochondrial respiration chain. Although environmental pollution has been postulated as a causal factor for the increasing prevalence of obesity, the role of rotenone in the pathogenesis of obesity has not been studied. We employed muscle-derived cell C2C12 as a model and shotgun lipidomics as a tool for lipid analysis and found that treatment of rotenone led to the profound deposition of intracellular triacylglycerol (TAG) in a time- and dose-dependent fashion. The TAG deposition was resulted from complex I inhibition. Further studies revealed that rotenone induced mitochondrial stress including decreased mitochondrial oxygen consumption rate, increased NADH/NAD+ ratio (i.e., reductive stress) and mitochondrial metabolites. We demonstrated that rotenone activated fatty acid de novo synthesis and TAG synthesis and ultimately resulted in intracellular TAG deposition. These studies suggested that increased mitochondrial stresses might be an underlying mechanism responsible for TAG accumulation manifest in obesity.
登录
查看更多内容
影响因子：
15.9
作者：
Kirby, DM;Salemi, R;Thorburn, DR
通讯作者：
Thorburn, DR
影响因子：
24
作者：
Niemann, Bernd;Chen, Ying;Rohrbach, Susanne
通讯作者：
Rohrbach, Susanne
DOI：
10.1073/pnas.1307237110
发表时间：
2013-05-28
影响因子：
11.1
作者：
Kamphorst, Jurre J.;Cross, Justin R.;Rabinowitz, Joshua D.
通讯作者：
Rabinowitz, Joshua D.
影响因子：
4.6
作者：
Deng, Yea-Tzy;Huang, Hsiu-Chen;Lin, Jen-Kun
通讯作者：
Lin, Jen-Kun
影响因子：
4.3
作者：
Moraes, CT;Diaz, F;Barrientos, A
通讯作者：
Barrientos, A