α-tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-α

Senthil Kumar Venugopal, Sridevi Devaraj, Teddy Yang, Ishwarlal Jialal

Research output: Contribution to journalArticle

153 Scopus citations

Abstract

Diabetes is a major risk factor for premature atherosclerosis, and oxidative stress appears to be an important mechanism. Previously, we showed that diabetic monocytes produce increased superoxide anion (O2 -), and α-tocopherol (AT) supplementation decreases this. The aim of this study was to elucidate the mechanism(s) of O2 - release and inhibition by AT under hyperglycemic (HG) conditions in monocytes. O2 - release, protein kinase C (PKC) activity, and translocation of PKC-α and -βII and p47phox were increased in THP-1 cells (human monocytic cell line) under HG (15 mmol/l glucose) conditions, whereas AT supplementation inhibited these changes. AT, NADPH oxidase inhibitors (apocynin and diphenyleneiodonium chloride [DPI]), and an inhibitor to PKC-α and other isoforms (2,2′,3,3′,4,4′-hexahydroxy-1,1′-biphenyl-6, 6′-dimethanol dimethyl ether [HBDDE]) but not PKC-β II (LY379196) decreased O2 - release and p47phox translocation. Antisense oligodeoxynucleotides to PKC-α and p47phox but not to PKC-βII inhibited HG-induced O2 - release and p47phox translocation in THP-1 cells. Under HG conditions, reactive oxygen species release from monocytes was not inhibited by agents affecting mitochondrial metabolism but was inhibited in human endothelial cells. We conclude that under HG conditions, monocytic O2 - release is dependent on NADPH oxidase activity but not the mitochondrial respiratory chain; HG-induced O2 - release is triggered by PKC-α, and AT inhibits O2 - release via inhibition of PKC-α.

Original languageEnglish (US)
Pages (from-to)3049-3054
Number of pages6
JournalDiabetes
Volume51
Issue number10
StatePublished - Oct 1 2002

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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