This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Khachigian, L. M. Articles by Fries, J. W. Search for Related Content PubMed PubMed Citation Articles by Khachigian, L. M. Articles by Fries, J. W.

American Journal of Pathology, Vol 151, 1225-1229, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

N-acetyl cysteine blocks mesangial VCAM-1 and NF-kappa B expression in vivo

LM Khachigian, T Collins and JW Fries
Centre for Thrombosis and Vascular Research, School of Pathology, University of New South Wales, Sydney, Australia.

Inducible vascular cell adhesion molecule-1 (VCAM-1) in glomerular mesangial cells (GMC) exposed to lipopolysaccharide (LPS) in vitro involves the activation of nuclear factor-kappa B (NF-kappa B) and its interaction with the proximal VCAM-1 promoter. We used a murine model to assess the effect of the antioxidant, N-acetyl cysteine on GMC activation in vivo. Single intraperitoneal administration of N-acetyl cysteine completely suppressed LPS-induced VCAM-1 expression on the GMC surface. When an oligonucleotide spanning the NF-kappa B binding region of the VCAM-1 promoter was incubated with extracts from the renal cortex of LPS-treated animals, a single nucleoprotein complex formed. This complex was composed of p50 and p65, but not p52, c-Rel, or RelB, and its formation was dramatically inhibited by pretreatment with N- acetyl cysteine, D,L-Buthionine-[S,R]-sulfoximide, a compound that depletes glutathione, augmented VCAM-1 expression inducible with a suboptimal amount of LPS to levels comparable with using 50 micrograms of LPS alone, D,L-Buthionine-[S,R]-sulfoximide also potentiated the p50- p65 binding activity induced with a suboptimal amount of LPS. These data provide a redox-sensitive, transcriptional link between NF-kappa B and VCAM-1 in GMC in vivo and implicate oxidative stress as an important regulatory signal in the pathogenesis of glomerular mesangial cell disorders.

This article has been cited by other articles:

				K. E. A. Burns, M. W. A. Chu, R. J. Novick, S. A. Fox, K. Gallo, C. M. Martin, L. W. Stitt, A. P. Heidenheim, M. L. Myers, and L. Moist Perioperative N-acetylcysteine to Prevent Renal Dysfunction in High-Risk Patients Undergoing CABG Surgery: A Randomized Controlled Trial JAMA, July 20, 2005; 294(3): 342 - 350. [Abstract] [Full Text] [PDF]

				P. Keshavan, T. L. Deem, S. J. Schwemberger, G. F. Babcock, J. M. Cook-Mills, and S. D. Zucker Unconjugated Bilirubin Inhibits VCAM-1-Mediated Transendothelial Leukocyte Migration J. Immunol., March 15, 2005; 174(6): 3709 - 3718. [Abstract] [Full Text] [PDF]

				K.-P. Chuang, Y.-F. Huang, Y.-L. Hsu, H.-S. Liu, H.-C. Chen, and C.-C. Shieh Ligation of lymphocyte function-associated antigen-1 on monocytes decreases very late antigen-4-mediated adhesion through a reactive oxygen species-dependent pathway Blood, December 15, 2004; 104(13): 4046 - 4053. [Abstract] [Full Text] [PDF]

				T. G. Gleeson and S. Bulugahapitiya Contrast-Induced Nephropathy Am. J. Roentgenol., December 1, 2004; 183(6): 1673 - 1689. [Full Text] [PDF]

				T. Laragione, V. Bonetto, F. Casoni, T. Massignan, G. Bianchi, E. Gianazza, and P. Ghezzi Redox regulation of surface protein thiols: Identification of integrin {alpha}-4 as a molecular target by using redox proteomics PNAS, December 9, 2003; 100(25): 14737 - 14741. [Abstract] [Full Text] [PDF]

				J. W. U. Fries, T. Roth, H.-P. Dienes, M. Weber, and M. Odenthal A novel evaluation method for paraffinized human renal biopsies using quantitative analysis of microdissected glomeruli and VCAM-1 as marker of inflammatory mesangial cell activation Nephrol. Dial. Transplant., April 1, 2003; 18(4): 710 - 716. [Abstract] [Full Text] [PDF]

				A. Zernecke, K. S. C. Weber, and C. Weber Combined modulation of the mesangial machinery for monocyte recruitment by inhibition of NF-kappa B Am J Physiol Cell Physiol, December 1, 2001; 281(6): C1881 - C1888. [Abstract] [Full Text] [PDF]

				M. J. Burne, A. Elghandour, M. Haq, S. R. Saba, J. Norman, T. Condon, F. Bennett, and H. Rabb IL-1 and TNF independent pathways mediate ICAM-1/VCAM-1 up-regulation in ischemia reperfusion injury J. Leukoc. Biol., August 1, 2001; 70(2): 192 - 198. [Abstract] [Full Text] [PDF]

				M. Tepel, M. van der Giet, C. Schwarzfeld, U. Laufer, D. Liermann, and W. Zidek Prevention of Radiographic-Contrast-Agent-Induced Reductions in Renal Function by Acetylcysteine N. Engl. J. Med., July 20, 2000; 343(3): 180 - 184. [Abstract] [Full Text] [PDF]

				K. Kuhn, S. Hashimoto, and M. Lotz IL-1{beta} Protects Human Chondrocytes from CD95-Induced Apoptosis J. Immunol., February 15, 2000; 164(4): 2233 - 2239. [Abstract] [Full Text] [PDF]

				C. D. Collard, A. Agah, W. Reenstra, J. Buras, and G. L. Stahl Endothelial Nuclear Factor-{kappa}B Translocation and Vascular Cell Adhesion Molecule-1 Induction by Complement : Inhibition With Anti-Human C5 Therapy or cGMP Analogues Arterioscler. Thromb. Vasc. Biol., November 1, 1999; 19(11): 2623 - 2629. [Abstract] [Full Text] [PDF]

				B. Jiang, M. Haverty, and P. Brecher N-Acetyl-L-Cysteine Enhances Interleukin-1{beta}-Induced Nitric Oxide Synthase Expression Hypertension, October 1, 1999; 34(4): 574 - 579. [Abstract] [Full Text] [PDF]

				S. Kokura, R. E. Wolf, T. Yoshikawa, D. N. Granger, and T. Y. Aw Molecular Mechanisms of Neutrophil-Endothelial Cell Adhesion Induced by Redox Imbalance Circ. Res., March 19, 1999; 84(5): 516 - 524. [Abstract] [Full Text] [PDF]