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(Hypertension. 2000;35:914.)
© 2000 American Heart Association, Inc.

Scientific Contributions

N-Acetyl-L-Cysteine Potentiates Interleukin-1ß Induction of Nitric Oxide Synthase

Role of p44/42 Mitogen-Activated Protein Kinases

Bingbing Jiang; Peter Brecher

From the Department of Biochemistry and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass.

Correspondence to Peter Brecher, PhD, Department of Biochemistry and Whitaker Cardiovascular Institute, Boston University School of Medicine, 80 E Concord St, Boston, MA 02118. E-mail pbrecher{at}acs.bu.edu

Abstract—We have reported previously that N-acetyl-L-cysteine facilitated interleukin-1ß–induced nitric oxide synthase (iNOS) expression in rat vascular smooth muscle cells. The present study compares the effect of N-acetyl-L-cysteine with other antioxidants and tested the possibility that N-acetyl-L-cysteine potentiates iNOS induction by a mechanism involving activation of p44/42 mitogen-activated protein kinases (MAPKs). The effect of N-acetyl-L-cysteine on potentiating interleukin-1ß–induced nitrite production and iNOS expression was mimicked either by the enantiomers, L-cysteine and D-cysteine, or by a non–thiol-containing antioxidant, L-ascorbic acid. Interleukin-1ß activated p44/42 MAPK, and this activation was enhanced in the presence of N-acetyl-L-cysteine. Inhibition of p44/42 MAPK phosphorylation by the selective inhibitor PD98059 clearly inhibited iNOS expression induced by interleukin-1ß either in the absence or in the presence of N-acetyl-L-cysteine. These observations, combined with previous results, indicate that p44/42 MAPK activation is required for interleukin-1ß induction of iNOS and that N-acetyl-L-cysteine may act as a reducing agent and facilitate interleukin-1ß–induced iNOS expression through a reduction/oxidation-related mechanism involving potentiation of cytokine activation of the p44/42 MAPK signaling pathway.

Key Words: acetylcysteine • interleukins • nitric oxide synthase • protein kinases • muscle, smooth, vascular

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