Melatonin Improves Mitochondrial Function by Promoting MT1/SIRT1/PGC-1 Alpha-Dependent Mitochondrial Biogenesis in Cadmium-Induced Hepatotoxicity In Vitro

• DOI: 10.1093/toxsci/kfu164
• Publication Date: 2014-08-27T05:04:30Z
• Authors: Pan Guo; Huifeng Pi; Shangcheng Xu; Lei Zhang; Yuming Li; Min Li; Zhengwang Cao; Li Tian; Jia Xie; Renyan Li; Mindi He; Yonghui Lu; Chuan Liu; Weixia Duan; Zhengping Yu; Zhou Zhou
• Keywords: Luzindole; Sirtuin 1; SIRT3; Cadmium chloride

Melatonin is an indolamine synthesized in the pineal gland that has a wide range of physiological functions, and it been under clinical investigation for expanded applications. Increasing evidence demonstrates melatonin can ameliorate cadmium-induced hepatotoxicity. However, potentially protective effects against hepatotoxicity underlying mechanisms this protection remain unclear. This study investigates pretreatment on elucidates potential mechanism melatonin-mediated protection. We exposed HepG2 cells to different concentrations cadmium chloride (2.5, 5, 10μM) 12 h. found Cd stimulated cytotoxicity, disrupted mitochondrial membrane potential, increased reactive oxygen species production, decreased mass DNA content. Consistent with finding, exposure was associated Sirtuin 1 (SIRT1) protein expression activity, thus promoted acetylation PGC-1 alpha, key enzyme involved biogenesis function, although did not disrupt interaction between SIRT1 alpha. all oxidative injuries were efficiently attenuated by pretreatment. Moreover, Sirtinol siRNA each blocked elevation function inhibiting SIRT1/ alpha signaling. Luzindole, receptor antagonist, partially block ability promote In summary, our results indicate plays essential role moderate stimulate improve at least through receptors