The role of mitochondrial complex III in melatonin-induced ROS production in cultured mesangial cells.
Melatonin is a potent scavenger of reactive oxygen (ROS) and reactive nitrogen species (RNS). At pharmacological concentrations, however, melatonin is documented to cause ROS/RNS production, especially in cultured cancerous cells. Currently, the mechanism responsible for melatonin-induced ROS generation remains elusive. In this study, we provided evidence that melatonin, at micromolar concentrations, induced rapid ROS generation by a mitochondrial-dependent mechanism in primary human mesangial (HM) cells. The melatonin-induced ROS production occurred independent of changes in Ca(2+) concentrations in the cytosol and/or in mitochondria. In mitochondria isolated from HM cells and mice kidney tissues, melatonin caused ROS production; this melatonin response was completely blocked by the complex III inhibitor antimycin A. In contrast, both the mitochondrial complex I inhibitor, rotenone, and another complex III inhibitor, myxothiazol, which interacts with complex III at a distinct site, had no significant inhibitory effect on melatonin-induced ROS generation. These results demonstrate that melatonin induced rapid ROS generation via the antimycin A-sensitive site of mitochondrial complex III.
Zhang
Hong-Mei
HM
Departments of MedicinePhysiology, University of Texas Health Science Center at San Antonio, Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, Audie L Murphy Division, San Antonio, TX 78229, USA.
Zhang
Yiqiang
Y
Zhang
Bin-Xian
BX
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D014450:Electron Transport Complex III / Q000378:metabolism*; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014450:Electron Transport Complex III; D008550:Melatonin; D002118:Calcium