HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Yang, F. Articles by Brüne, B. Search for Related Content PubMed PubMed Citation Articles by Yang, F. Articles by Brüne, B.

(Journal of Leukocyte Biology. 2000;68:916-922.)
© 2000 by Society for Leukocyte Biology

Modulation of nitric oxide-evoked apoptosis by the p53-downstream target p21^WAF1/CIP1

Fan Yang^*, Andreas von Knethen and Bernhard Brüne

University of Erlangen-Nürnberg, Faculty of Medicine, Department of Medicine IV-Experimental Division, 91054 Erlangen, Germany; and
^* The Fourth Military Medical University, Department of Pathology, Xi’an, 710032, China

Correspondence: Bernhard Brüne, University of Erlangen-Nürnberg, Faculty of Medicine, Loschgestrasse 8, 91054 Erlangen, Germany. E-mail: mfm423{at}rzmail.uni-erlangen.de

When produced in excess, the inflammatory mediator nitric oxide (NO) attenuates cell-cycle progression at the G1 phase in tight correlation with p21^WAF1/CIP1 expression, provokes accumulation of the tumor suppressor p53, and initiates apoptosis/necrosis as judged on cell accumulation in the sub-G1 phase. To verify the role of p21^WAF1/CIP1 in modulating cell-cycle arrest vs. apoptosis, we transfected stably antisense p21^WAF1/CIP1-encoding plasmids. Following NO exposure, accumulation of p21^WAF1/CIP1, but not p53, was largely attenuated in antisense p21^WAF1/CIP1 transfectants. Moreover, the G1 cell-cycle arrest was abrogated, and cells were sensitized toward apoptosis compared with parent macrophages. In contrast, antisense elimination of p53 attenuated p53 as well as p21^WAF1/CIP1 expression, abolished the G1 cell-cycle arrest, and prevented apoptosis. We conclude that p21^WAF1/CIP1 is a downstream target of p53 in macrophages that modulate the sensitivity toward the immune-modulator NO.

Key Words: p21^WAF1/CIP1 • p53 • NO • apoptosis • cell cycle • macrophages

This article has been cited by other articles:

				I. V. Smirnova, M. Kajstura, T. Sawamura, and M. S. Goligorsky Asymmetric dimethylarginine upregulates LOX-1 in activated macrophages: role in foam cell formation Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H782 - H790. [Abstract] [Full Text] [PDF]

				S. Hortelano, P. G. Traves, M. Zeini, A. M. Alvarez, and L. Bosca Sustained Nitric Oxide Delivery Delays Nitric Oxide-Dependent Apoptosis in Macrophages: Contribution to the Physiological Function of Activated Macrophages J. Immunol., December 1, 2003; 171(11): 6059 - 6064. [Abstract] [Full Text] [PDF]

				A. L. Gartel and A. L. Tyner The Role of the Cyclin-dependent Kinase Inhibitor p21 in Apoptosis Mol. Cancer Ther., June 1, 2002; 1(8): 639 - 649. [Abstract] [Full Text] [PDF]