Am J Physiol Cell Physiol Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol (October 3, 2001). doi:10.1152/ajpcell.00119.2001
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
282/3/C625    most recent
00119.2001v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kibbe, M. R
Right arrow Articles by Tzeng, E.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Kibbe, M. R
Right arrow Articles by Tzeng, E.

Articles in PresS, published online ahead of print October 3, 2001
Am J Physiol Cell Physiol, 10.1152/ajpcell.00119.2001
Submitted on March 8, 2001
Accepted on September 10, 2001

Potentiation of nitric oxide-induced apoptosis in p53-/- vascular smooth muscle cells

Melina R Kibbe1*, Jianrong Li1, Suhua Nie1, Byung M Choi1, Imre Kovesdi2, Alena Lizonova2, Timothy R Billiar1, and Edith Tzeng1

1 Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
2 GenVec Inc., Gaithersburg, MD, USA

* To whom correspondence should be addressed. E-mail: kibbemr{at}msx.upmc.edu.

The functional role of p53 in NO-mediated VSMC apoptosis remains unknown. In this study, VSMC from p53-/- and p53+/+ murine aortae were exposed to exogenous or endogenous sources of NO. Unexpectedly, p53-/- VSMC were much more sensitive to the pro-apoptotic effects of NO than p53+/+ VSMC. Furthermore, this paradox appeared to be specific to NO as other pro-apoptotic agents did not demonstrate this differential effect on p53-/- cells. NO-induced apoptosis in p53-/- VSMC occurred independent of cGMP generation. However, mitogen-activated protein kinase (MAPK) pathways appeared to play a significant role. Treatment of the p53-/- VSMC with SNAP resulted in a marked activation of p38 MAPK and, to a lesser extent, of JNK, MEK1/2, and p42/44(ERK). Furthermore, basal activity of the MEK-p42/44(ERK) pathway was increased in the p53+/+ VSMC. Inhibition of p38 MAPK with SB203580, or MEK1/2 with PD98059 blocked NO-induced apoptosis. Therefore, p53 may protect VSMC against NO-mediated apoptosis, in part, through differential regulation of MAPK pathways.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. S. Ahanchi, V. N. Varu, N. D. Tsihlis, J. Martinez, C. G. Pearce, M. R. Kapadia, Q. Jiang, J. E. Saavedra, L. K. Keefer, J. A. Hrabie, et al.
Heightened efficacy of nitric oxide-based therapies in type II diabetes mellitus and metabolic syndrome
Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2388 - H2398.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. M. McLaughlin and B. Demple
Nitric Oxide-Induced Apoptosis in Lymphoblastoid and Fibroblast Cells Dependent on the Phosphorylation and Activation of p53
Cancer Res., July 15, 2005; 65(14): 6097 - 6104.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. Mizuno, M. Kadowaki, Y. Demura, S. Ameshima, I. Miyamori, and T. Ishizaki
p42/44 Mitogen-Activated Protein Kinase Regulated by p53 and Nitric Oxide in Human Pulmonary Arterial Smooth Muscle Cells
Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2): 184 - 192.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
B. Tian, J. Liu, P. B. Bitterman, and R. J. Bache
Mechanisms of cytokine induced NO-mediated cardiac fibroblast apoptosis
Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1958 - H1967.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.