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Neuronal nitric oxide synthase (NOS) regulates the expression of inducible NOS in rat small intestine via modulation of nuclear factor kappa B
Author(s) -
QU XIAOWU,
WANG HAO,
DE PLAEN ISABELLE G.,
ROZENFELD RANNA A.,
HSUEH WEI
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.99-0343com
Subject(s) - nitric oxide synthase , nitric oxide , chemistry , pyrrolidine dithiocarbamate , nf κb , endothelial nos , nfkb1 , medicine , small intestine , endocrinology , microbiology and biotechnology , biology , biochemistry , signal transduction , transcription factor , enos , gene
We previously reported that neuronal nitric oxide synthase (nNOS) is the predominant NOS in the intestine. Inducible NOS (iNOS), an enzyme involved in the inflammatory response, is regulated by cytokines via the transcriptional factor NF‐κB. We examined a new mechanism of intestinal iNOS regulation with respect to the role of nNOS and its effect on NF‐κB. Young Sprague‐Dawley rats were treated for 4 days with 1) saline, 2) 7‐nitroindazole (7‐NI, specific nNOS inhibitor), 3) 7‐NI + pyrrolidine dithiocarbam‐ate (PDTC, NF‐κB inhibitor), or 4) PDTC. Intestinal iNOS mRNA, NF‐κB activity, and the tissue content of the regulatory IκBα were examined. We found that 7‐NI‐treated animals had higher intestinal NF‐κB (p50‐p65) activity, lower IκB α content, and increased intestinal iNOS mRNA, iNOS protein, and iNOS activity compared with controls. All of these changes were abolished when PDTC was given together with 7‐NI. PDTC alone had no effect. 7‐NI induces a delayed increase in intestinal myeloperoxidase activity (after elevation in NF‐κB and iNOS), which could be abrogated by PDTC. We conclude that in normal rat small intestine, nNOS suppresses the gene expression of iNOS through NF‐κB down‐regulation and that nNOS suppression leads to IκBα degradation, NF‐κB activation, and iNOS expression.—Qu, X.‐w., Wang, H., De Plaen, I. G., Rozenfeld, R. A., Hsueh, W. Neuronal nitric oxide synthase (NOS) regulates the expression of inducible NOS in rat small intestine via modulation of nuclear factor kappa B. FASEB J. 15, 439‐446 (2001)