Impaired mitochondrial complex III and melatonin responsive reactive oxygen species generation in kidney mitochondria of db/db mice

Hua Zhang, Hong Mei Zhang, Li Ping Wu, Dun Xian Tan, Amrita Kamat, Yun Qing Li, Michael S. Katz, Hanna E. Abboud, Russel J. Reiter, Bin Xian Zhang

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

We have previously demonstrated that melatonin, at pharmacological concentrations, causes rapid reactive oxygen species (ROS) generation at the antimycin-A sensitive site of mitochondrial complex III (MC-3). In the current work, we used this melatonin response to investigate the role of mitochondrial dysfunction in the development of diabetic nephropathy. We find that the development of diabetic nephropathy, as indicated by hyperfiltration and histopathological lesions in the kidney of db/db mice, is associated with diminished melatonin-induced ROS generation and MC-3 activity, indicating impaired MC-3 at the antimycin-A site. The MC-3 protein level in the renal mitochondria was equivalent in db/db and the nondiabetic db/m mice, whereas mitochondrial complex I (MC-1) protein was dramatically upregulated in the db/db mice. This differential regulation in mitochondrial complexes may alter the equilibrium of the electron transport in renal mitochondria and contribute to ROS overproduction. The study provides one mechanism of enhanced oxidative stress that may be involved in the pathogenesis of diabetic nephropathy in db/db mice.

Original languageEnglish (US)
Pages (from-to)338-344
Number of pages7
JournalJournal of pineal research
Volume51
Issue number3
DOIs
StatePublished - Oct 2011

Keywords

  • diabetic nephropathy
  • glomerular filtration rate
  • hyperfiltration
  • melatonin
  • mitochondria
  • mitochondrial complex I and III
  • reactive oxygen species

ASJC Scopus subject areas

  • Endocrinology

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