Lipoic acid-mediated signal transduction

Susan Shi, R. M. Day, M. Chedid, J. B. Blumberg, Y. J. Suzuki

Research output: Contribution to journalArticle

Abstract

We found, in NIH/3T3 cells, that α-lipoic acid (ALA), a thiol antioxidant as well as a co-factor for mitochondrial dehydrogenases, activated p44/42 MAP kinase. Cells were serum-starved for 2 h with or without ALA, cell lysates prepared, and activation of MAP kinase determined by Western blot analysis using antibody for phosphorylated MAP kinase (Tyr204). Treatment of cells with ALA (20nM - 20μm) resulted in concentration- and time-dependent, increase in phosphorylated MAP kinase with maximal activation reached at 1-2 h. Slow activation of MAP kinase by ALA may reflect the involvement of glutathione synthesis since N-acetylcysteine also activated MAP kinase although mM concentrations were needed. Activation of MAP kinase by these thiols was blocked by dominant negative mutant of p21ras, suggesting the involvement of Ras GTPase. ALA-induction of p21ras-signaling for MAP kinase phosphorylation is independent of Ca2+-signaling since neither BAPTA-AM nor W-7 had inhibitory effects. Activation of Ras-MAP kinase pathways may be the mechanism of ALA-dependent cell growth which we have previously observed in vascular smooth muscle cells.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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