Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes: Role of vascular NAD(P)H oxidase

Toyoshi Inoguchi, Toshiyo Sonta, Hirotaka Tsubouchi, Takashi Etoh, Maiko Kakimoto, Noriyuki Sonoda, Naoichi Sato, Naotaka Sekiguchi, Kunihisa Kobayashi, Hideki Sumimoto, Hideo Utsumi, Hajime Nawata

Research output: Contribution to journalArticlepeer-review

325 Citations (Scopus)

Abstract

Hyperglycemia seems to be an important causative factor in the development of micro- and macrovascular complications in patients with diabetes. Several hypotheses have been proposed to explain the adverse effects of hyperglycemia on vascular cells. Both protein kinase C (PKC) activation and oxidative stress theories have increasingly received attention in recent years. This article shows a PKC-dependent increase in oxidative stress in diabetic vascular tissues. High glucose level stimulated reactive oxygen species (ROS) production via a PKC-dependent activation of NAD(P)H oxidase in cultured aortic endothelial cells, smooth muscle cells, and renal mesangial cells. In addition, expression of NAD(P)H oxidase components were shown to be upregulated in vascular tissues and kidney from animal models of diabetes. Furthermore, several agents that were expected to block the mechanism of a PKC-dependent activation of NAD(P)H oxidase clearly inhibited the increased oxidative stress in diabetic animals, as assessed by in vivo electron spin resonance method. Taken together, these findings strongly suggest that the PKC-dependent activation of NAD(P)H oxidase may be an essential mechanism responsible for increased oxidative stress in diabetes.

Original languageEnglish
Pages (from-to)S227-S232
JournalJournal of the American Society of Nephrology
Volume14
Issue numberSUPPL. 3
Publication statusPublished - Aug 1 2003

All Science Journal Classification (ASJC) codes

  • Nephrology

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