JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yue, G.
Right arrow Articles by Y-K. Wong, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yue, G.
Right arrow Articles by Y-K. Wong, P.

Vol. 297, Issue 3, 915-925, June 2001

Colon Epithelial Cell Death in 2,4,6-Trinitrobenzenesulfonic Acid-Induced Colitis Is Associated with Increased Inducible Nitric-Oxide Synthase Expression and Peroxynitrite Production

Gang Yue, Pi-Shiang Lai, Kingsley Yin, Frank F. Sun, Robert G. Nagele, Xiao Liu, Kersti K. Linask, Congli Wang, King-Teh Lin and Patrick Y-K. Wong

Departments of Cell Biology (G.Y., P.-S.L., K.Y., F.F.S., X.L., K.K.L., C.W., K.-T.L., P.Y.-K.W.) and Molecular Biology (R.G.N.), School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey

Peroxynitrite, derived from the reaction of nitric oxide (NO·) with superoxide (O&cjs1138;2), is a potent nitrating and oxidizing agent that can induce apoptosis in a variety of different cell types. In the present study, we investigated the possible role of peroxynitrite as a mediator of colon epithelial cell death in rat colitis. Rat colon inflammation was induced by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) and rats were sacrificed 24 h after TNBS administration. Expression of inducible nitric-oxide synthase (iNOS) was detected by reverse transcription-polymerase chain reaction and immunohistochemistry. The enzymatic activities of Ca2+-independent iNOS and Ca2+-dependent constitutive nitric-oxide synthase were determined biochemically. Evidence of peroxynitrite-mediated cell injury was detected by immunostaining of nitrotyrosine. Apoptosis was examined by in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and DNA gel electrophoresis. To evaluate the specific contribution of peroxynitrite to the observed cell injury, a selective iNOS inhibitor, L-NG-[1-iminoethyl]lysine (L-NIL), was administered after TNBS induction. Morphological examination and analysis of TUNEL/cytokeratin double immunofluorescence revealed significant apoptosis in mucosal epithelial cells. Nitrotyrosine was colocalized with TUNEL, strongly demonstrating the association of peroxynitrite with the apoptotic death of colon epithelial cells. The administration of L-NIL reduced iNOS activity in 24-h lesions by 92% and also significantly attenuated both nitrotyrosine staining and apoptotic cell counts in the colon epithelium. These results strongly suggest that local elevated level of peroxynitrite produced from increased iNOS expression and activity is a major contributor to colon epithelial apoptosis during colon inflammation.

0022-3565/01/2973-0915$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
P. Pacher, J. S. Beckman, and L. Liaudet
Nitric Oxide and Peroxynitrite in Health and Disease
Physiol Rev, January 1, 2007; 87(1): 315 - 424.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
Y. Vera, K. Erkkila, C. Wang, C. Nunez, S. Kyttanen, Y. Lue, L. Dunkel, R. S. Swerdloff, and A. P. Sinha Hikim
Involvement of p38 Mitogen-Activated Protein Kinase and Inducible Nitric Oxide Synthase in Apoptotic Signaling of Murine and Human Male Germ Cells after Hormone Deprivation
Mol. Endocrinol., July 1, 2006; 20(7): 1597 - 1609.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. L. Gookin, S. Chiang, J. Allen, M. U. Armstrong, S. H. Stauffer, C. Finnegan, and M. P. Murtaugh
NF-{kappa}B-mediated expression of iNOS promotes epithelial defense against infection by Cryptosporidium parvum in neonatal piglets
Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G164 - G174.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
J. L. Gookin, J. Allen, S. Chiang, L. Duckett, and M. U. Armstrong
Local Peroxynitrite Formation Contributes to Early Control of Cryptosporidium parvum Infection
Infect. Immun., July 1, 2005; 73(7): 3929 - 3936.
[Abstract] [Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
A. P. S. Hikim, Y. Vera, D. Vernet, M. Castanares, M. Diaz-Romero, M. Ferrini, R. S. Swerdloff, N. F. Gonzalez-Cadavid, and C. Wang
Involvement of Nitric Oxide-Mediated Intrinsic Pathway Signaling in Age-Related Increase in Germ Cell Apoptosis in Male Brown-Norway Rats
J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2005; 60(6): 702 - 708.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
J. Segui, M. Gironella, M. Sans, S. Granell, F. Gil, M. Gimeno, P. Coronel, J. M. Pique, and J. Panes
Superoxide dismutase ameliorates TNBS-induced colitis by reducing oxidative stress, adhesion molecule expression, and leukocyte recruitment into the inflamed intestine
J. Leukoc. Biol., September 1, 2004; 76(3): 537 - 544.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. L. Gookin, L. L. Duckett, M. U. Armstrong, S. H. Stauffer, C. P. Finnegan, M. P. Murtaugh, and R. A. Argenzio
Nitric oxide synthase stimulates prostaglandin synthesis and barrier function in C. parvum-infected porcine ileum
Am J Physiol Gastrointest Liver Physiol, September 1, 2004; 287(3): G571 - G581.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
C. L. Green, W. Ho, K. A. Sharkey, and D. M. McKay
Dextran sodium sulfate-induced colitis reveals nicotinic modulation of ion transport via iNOS-derived NO
Am J Physiol Gastrointest Liver Physiol, September 1, 2004; 287(3): G706 - G714.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
X. Gu, A. B. El-Remessy, S. E. Brooks, M. Al-Shabrawey, N.-T. Tsai, and R. B. Caldwell
Hyperoxia induces retinal vascular endothelial cell apoptosis through formation of peroxynitrite
Am J Physiol Cell Physiol, September 1, 2003; 285(3): C546 - C554.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. C. Montalto, M. L. Hart, J. E. Jordan, K. Wada, and G. L. Stahl
Role for complement in mediating intestinal nitric oxide synthase-2 and superoxide dismutase expression
Am J Physiol Gastrointest Liver Physiol, June 9, 2003; 285(1): G197 - G206.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics.