CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dimmeler, S.
Right arrow Articles by Zeiher, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dimmeler, S.
Right arrow Articles by Zeiher, A. M.

Cell Growth & Differentiation, Vol 9, Issue 5 415-422, Copyright © 1998 by American Association of Cancer Research


ARTICLES

Nitric oxide inhibits APO-1/Fas-mediated cell death

S Dimmeler, J Haendeler, A Sause and AM Zeiher
Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany.

Activation of the cysteine protease caspases, which are homologous to the product of Caenorhabditis elegans cell-death gene ced 3, is required to mediate APO-1/Fas-induced apoptosis. We report here that nitric oxide (NO) released by exogenous NO donors, as well as NO endogenously derived by transfection with the inducible NO synthase, substantially suppresses APO-1/Fas-triggered cell death of Jurkat cells. The inhibitory NO effect was independent of cGMP, because 8-bromo-cGMP did not influence APO-1/Fas-mediated apoptosis. In contrast, NO interferes with the APO-1/Fas-induced stimulation of caspases. NO inhibits the proteolytic cleavage of caspase-3 (CPP32) into its active subunits, thereby suppressing caspase-3 activity. In addition, NO potently inhibits apoptosis induction by overexpresssion of the death domain protein FADD or the immediate downstream target caspase-8. These results suggest that NO modulates the proteolytic cascade upstream of caspase-3. Indeed, NO specifically S-nitrosylates caspase-8 and caspase-1 and thereby may prevent activation of the proteolytic cascade. The NO-mediated increase in the resistance toward induction of apoptosis may play a major role in mediating immune responses, as well as in the pathogenesis of autoimmune diseases.


This article has been cited by other articles:


Home page
Molecular Cancer TherapeuticsHome page
L. Booth, J. L. Roberts, N. Cruickshanks, S. Grant, A. Poklepovic, and P. Dent
Regulation of OSU-03012 Toxicity by ER Stress Proteins and ER Stress-Inducing Drugs
Mol. Cancer Ther., October 1, 2014; 13(10): 2384 - 2398.
[Abstract] [Full Text] [PDF]


Home page
J. Leukoc. Biol.Home page
R. S. Mahidhara, R. A. Hoffman, S. Huang, A. Wolf-Johnston, Y. Vodovotz, R. L. Simmons, and T. R. Billiar
Nitric oxide-mediated inhibition of caspase-dependent T lymphocyte proliferation
J. Leukoc. Biol., September 1, 2003; 74(3): 403 - 411.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
J. Liu, J. E. Saavedra, T. Lu, J.-G. Song, J. Clark, M. P. Waalkes, and L. K. Keefer
O2-Vinyl 1-(Pyrrolidin-1-yl)diazen-1-ium-1,2-diolate Protection Against D-Galactosamine/Endotoxin-Induced Hepatotoxicity in Mice: Genomic Analysis Using Microarrays
J. Pharmacol. Exp. Ther., January 1, 2002; 300(1): 18 - 25.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
H. Zeng, N. Y. Spencer, and N. Hogg
Metabolism of S-nitrosoglutathione by endothelial cells
Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H432 - H439.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
P. Andreka, J. Zang, C. Dougherty, T. I. Slepak, K. A. Webster, and N. H. Bishopric
Cytoprotection by Jun Kinase During Nitric Oxide-Induced Cardiac Myocyte Apoptosis
Circ. Res., February 16, 2001; 88(3): 305 - 312.
[Abstract] [Full Text] [PDF]


Home page
JACCHome page
L. Rössig, J. Haendeler, Z. Mallat, B. Hugel, J.-M. Freyssinet, A. Tedgui, S. Dimmeler, and A. M. Zeiher
Congestive heart failure induces endothelial cell apoptosis: protective role of carvedilol
JACC, December 1, 2000; 36(7): 2081 - 2089.
[PDF]


Home page
J Biol ChemHome page
E. Hatano, C. A. Bradham, A. Stark, Y. Iimuro, J. J. Lemasters, and D. A. Brenner
The Mitochondrial Permeability Transition Augments Fas-induced Apoptosis in Mouse Hepatocytes
J. Biol. Chem., April 21, 2000; 275(16): 11814 - 11823.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. F. Romano, A. Lamberti, R. Bisogni, C. Garbi, A. M. Pagnano, P. Auletta, P. Tassone, M. C. Turco, and S. Venuta
Amifostine Inhibits Hematopoietic Progenitor Cell Apoptosis by Activating NF-kappa B/Rel Transcription Factors
Blood, December 15, 1999; 94(12): 4060 - 4066.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
C. Scaffidi, I. Schmitz, J. Zha, S. J. Korsmeyer, P. H. Krammer, and M. E. Peter
Differential Modulation of Apoptosis Sensitivity in CD95 Type I and Type II Cells
J. Biol. Chem., August 6, 1999; 274(32): 22532 - 22538.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
H. E. Thomas, R. Darwiche, J. A. Corbett, and T. W. H. Kay
Evidence That {beta} Cell Death in the Nonobese Diabetic Mouse Is Fas Independent
J. Immunol., August 1, 1999; 163(3): 1562 - 1569.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J. Li, C. A. Bombeck, S. Yang, Y.-M. Kim, and T. R. Billiar
Nitric Oxide Suppresses Apoptosis via Interrupting Caspase Activation and Mitochondrial Dysfunction in Cultured Hepatocytes
J. Biol. Chem., June 11, 1999; 274(24): 17325 - 17333.
[Abstract] [Full Text] [PDF]


Home page
ScienceHome page
J. B. Mannick, A. Hausladen, L. Liu, D. T. Hess, M. Zeng, Q. X. Miao, L. S. Kane, A. J. Gow, and J. S. Stamler
Fas-Induced Caspase Denitrosylation
Science, April 23, 1999; 284(5414): 651 - 654.
[Abstract] [Full Text]


Home page
J Biol ChemHome page
L. Rossig, B. Fichtlscherer, K. Breitschopf, J. Haendeler, A. M. Zeiher, A. Mulsch, and S. Dimmeler
Nitric Oxide Inhibits Caspase-3 by S-Nitrosationin Vivo
J. Biol. Chem., March 12, 1999; 274(11): 6823 - 6826.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1998 by the American Association of Cancer Research.