The role of mitochondrial complex III in melatonin-induced ROS production in cultured mesangial cells

Hong Mei Zhang, Yiqiang Zhang, Bin Xian Zhang

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)78-82
Number of pages5
JournalJournal of pineal research
Volume50
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • melatonin
  • mesangial cells
  • mitochondria
  • reactive oxygen species

ASJC Scopus subject areas

  • Endocrinology

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