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.
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.
Hong-Mei
HM
Zhang
Yiqiang
Y
Zhang
Bin-Xian
BX
Zhang
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