Rotenone is a mitochondrial electron transport chain complex I inhibitor that can induce apoptosis by enhancing the production of mitochondrial reactive oxygen species.
HL-60 cells were treated with rotenone (1 μ m ; 36 h) approximately 50% of HL-60 cells showed chromatin condensation and nuclear fragmentation under confocal microscopy[1].Rotenone(1μM/10 nM/100 nM;24-48h) causes dose-dependent cell death in SK-N-MC neuroblastoma cells[3].
Rotenone (2.5 mg/kg/day) for 4 weeks decreased the number of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the SNpc and signal intensity of TH in the striatum[2]. In the renal ischemia-reperfusion model, Rotenone(200ppm;3weeks) can protect renal tubules, block renal fibrosis, reduce inflammation and apoptosis, and improve mitochondrial abnormalities[4].
References:
[1]. Li N, Ragheb K, Lawler G, Sturgis J, Rajwa B, Melendez JA, Robinson JP. Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem. 2003 Mar 7;278(10):8516-25.
[2]. Miyazaki I, Isooka N, Imafuku F, Sun J, Kikuoka R, Furukawa C, Asanuma M. Chronic Systemic Exposure to Low-Dose Rotenone Induced Central and Peripheral Neuropathology and Motor Deficits in Mice: Reproducible Animal Model of Parkinson's Disease. Int J Mol Sci. 2020 May 4;21(9):3254.
[3] Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, Miller GW, Yagi T, Matsuno-Yagi A, Greenamyre JT. Mechanism of toxicity in rotenone models of Parkinson's disease. J Neurosci. 2003 Nov 26;23(34):10756-64.
[4] Zhang W, Sha Y, Wei K, Wu C, Ding D, Yang Y, Zhu C, Zhang Y, Ding G, Zhang A, Jia Z, Huang S. Rotenone ameliorates chronic renal injury caused by acute ischemia/reperfusion. Oncotarget. 2018 May 11;9(36):24199-24208.
Rotenone是一种线粒体电子传递链复合物 I 抑制剂，可通过增强线粒体活性氧的产生来诱导细胞凋亡。
用Rotenone（1μM；36h）处理HL-60细胞后，在共聚焦显微镜下，约50%的HL-60细胞出现染色质凝聚和核碎裂[1]。Rotenone（1μM/10 nM/100 nM；24-48h）导致SK-N-MC神经母细胞瘤细胞发生剂量依赖性细胞死亡[3]。
Rotenone（2.5 mg/kg/day）连续4周可减少黑质前核中酪氨酸羟化酶（TH）阳性多巴胺能神经元的数量和纹状体中TH的信号强度[2]。在肾缺血再灌注模型中，Rotenone（200ppm；3周）可保护肾小管，阻断肾纤维化，减少炎症和细胞凋亡，改善线粒体异常[4]。