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Hum. Reprod. Advance Access originally published online on February 16, 2006
Human Reproduction 2006 21(6):1605-1611; doi:10.1093/humrep/dei500
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Regulation of inducible nitric oxide synthase in post-operative adhesions

G.M. Saed1,3, M. Zhao1, M.P. Diamond1 and H.M Abu-Soud1,2

1 Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development and 2 Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI, USA

3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, The C.S. Mott Center for Growth and Development, Wayne State University School of Medicine, 275 E. Hancock, Detroit, MI 48201, USA. E-mail: gsaed{at}med.wayne.edu

BACKGROUND: The deficiency of the inducible nitric oxide synthase (iNOS) substrate, L-arginine (L-Arg), the co-factor tetrahydrobiopterin (H4B) or molecular oxygen may lead to lower NO levels, which enhances the development of adhesion phenotype. METHODS: We utilized high-performance liquid chromatography (HPLC) and immunoprecipitation with nitrotyrosine antibody to determine the levels of H4B, citrulline and protein nitration in fibroblasts established from normal peritoneal and adhesion tissues. RESULTS: The level of H4B was dramatically attenuated in adhesion fibroblasts. The immunoprecipitation with nitrotyrosine antibody revealed higher protein nitration in adhesion compared with normal fibroblasts. There were higher accumulations of citrulline in adhesion fibroblasts as compared with normal fibroblasts. In addition, peritoneal fibroblasts treated with 2% oxygen for 24 h and implanted back into the peritoneal cavity of the rats exhibited marked increase in severity of adhesion as well as extensive distribution involving many sites and organs. CONCLUSIONS: Control of the catalytic activity of iNOS in adhesion fibroblasts may be because of subsaturating amounts of L-Arg and H4B which allow iNOS to generate a combination of reactive oxygen species in addition to NO, thereby influencing NO bioavailability and function.

Key words: adhesions/L-arginine/nitric oxide synthase/surgery/tetrahydrobiopterin

Submitted on 30 June, 2005; resubmitted on 29 September, 2005, 22 November, 2005, 6 December, 2005 ; accepted on 22 December, 2005
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