雷公藤甲素
安普克
AMP活化蛋白激酶
维甲酸
线粒体
脂肪酸代谢
支持细胞
化学
β氧化
内分泌学
内科学
蛋白激酶A
新陈代谢
生物
磷酸化
生物化学
细胞凋亡
精子发生
医学
基因
作者
Yisen Cheng,Gaojian Chen,Li Wang,Jiamin Kong,Jisheng Pan,Yue Xi,Feihai Shen,Zhiying Huang
标识
DOI:10.1016/j.toxlet.2018.04.035
摘要
Triptolide is a major active ingredient of tripterygium glycosides, used for the therapy of immune and inflammatory diseases. However, its clinical applications are limited by severe male fertility toxicity associated with decreased sperm count, mobility and testicular injures. In this study, we determined that triptoide-induced mitochondrial dysfunction triggered reduction of lactate and dysregulation of fatty acid metabolism in mouse Sertoli cells. First, triptolide induced mitochondrial damage through the suppressing of proliferator-activated receptor coactivator-1 alpha (PGC-1α) activity and protein. Second, mitochondrial damage decreased lactate production and dysregulated fatty acid metabolism. Finally, mitochondrial dysfunction was initiated by the inhibition of sirtuin 1 (SIRT1) with the regulation of AMP-activated protein kinase (AMPK) in Sertoli cells after triptolide treatment. Meanwhile, triptolide induced mitochondrial fatty acid oxidation dysregulation by increasing AMPK phosphorylation. Taken together, we provide evidence that the mechanism of triptolide-induced testicular toxicity under mitochondrial injury may involve a metabolic change.
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