Document Detail

N-Acetyl-L-cysteine potentiates interleukin-1beta induction of nitric oxide synthase : role of p44/42 mitogen-activated protein kinases.
MedLine Citation:
PMID:  10775561     Owner:  NLM     Status:  MEDLINE    
We have reported previously that N-acetyl-L-cysteine facilitated interleukin-1beta-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-1beta-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-1beta 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-1beta 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-1beta induction of iNOS and that N-acetyl-L-cysteine may act as a reducing agent and facilitate interleukin-1beta-induced iNOS expression through a reduction/oxidation-related mechanism involving potentiation of cytokine activation of the p44/42 MAPK signaling pathway.
B Jiang; P Brecher
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  35     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-09     Completed Date:  2000-05-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  914-8     Citation Subset:  IM    
Department of Biochemistry and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.
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MeSH Terms
Acetylcysteine / pharmacology*
Cells, Cultured
Drug Synergism
Enzyme Induction / drug effects
Free Radical Scavengers / pharmacology*
Interleukin-1 / pharmacology*
MAP Kinase Signaling System / drug effects
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / metabolism*
Muscle, Smooth, Vascular / enzymology*
Nitric Oxide Synthase / metabolism*
Nitric Oxide Synthase Type II
Rats, Wistar
Grant Support
Reg. No./Substance:
0/Free Radical Scavengers; 0/Interleukin-1; 616-91-1/Acetylcysteine; EC Oxide Synthase; EC Oxide Synthase Type II; EC protein, rat; EC Protein Kinase 1; EC Protein Kinase 3; EC Protein Kinases

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