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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2004.1
- 수록면
- 311 - 324 (14page)
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초록· 키워드
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The expression of inducible nitric oxide synthase
(iNOS) is a critical factor in both normal
physiological functions and the pathogenesis of
disease. This study was undertaken to determine
the m olecular m echanism by which nitric
oxide (NO) exerts negative feedback regulation
on iNOS gene expression. Isolated rat hepatocytes
stimulated with cytokines exhibited a
marked increase in NO production as well as
iNOS mRNA and protein levels, which were
significantly reduced by pretreatment of the NO
donors S-nitroso-N-acetyl-D,L-penicillamine (SNAP)
and V-PYRRO/NO. This effect of SNAP was inhibited
when NO was scavenged using red
blood cells. Pretreatment with oxidized SNAP,
8-Br-cGMP, NO2
-, or NO3
- did not suppress the
cytokine-induced NO production. Moreover, LPS/
IFN- γ -stimulated RAW264.7 cells, which produce
endogenous NO, expressed lower levels of iNOS,
IL-1β, IL-6 and TNF-α mRNAs, without changes
in their mRNA half-lives, than those in the
presence of the iNOS inhibitor NG-monomethyl-
L-arginine. The iNOS gene transcription rate exhibited
an 18-fold increase after cytokine stimulation,
which was significantly inhibited by
SNAP pretreatment. SNAP also blocked cytokineinduced
increase in NF-κB activation, iNOS
promoter activity, nuclear translocation of cytosolic
NF-κB p65 subunit, and IκBα degradation,
which correlated with its inhibitory effect on
phosphorylation and ubiquitination of IκB. These
data indicate that NO down-regulates iNOS gene
expression and NO production by inhibiting the
post-translational processes of IκBα thereby preventing
NF-κB activation. These results identify
a novel negative feedback mechanism whereby
NO down-regulates iNOS gene expression.
목차
등록된 정보가 없습니다.
참고문헌 (29)
참고문헌 신청
/ / Inhibition of nitric oxide synthesis enhances the expressionof inducible nitric oxide synthase mRNA and protein ina model of chronic liver inflammation : 635 ~ 40
/ / and activity in humanlung epithelial cells : 10089 ~ 93
/ / in vivo expression ofinducible nitric oxide synthase in experimentally inducedneurologic diseases : 3024 ~ 7
/ 1995 / A central role for interleukin-1βin the in vitro and in vivo regulation of hepatic inducible nitricoxide synthase : 4890 ~ 8
/ 1995 / Induction of nitric oxide synthase mRNA expression : 26731 ~ 3
/ / and activity in humanlung epithelial cells : 10089 ~ 93
/ / in vivo expression ofinducible nitric oxide synthase in experimentally inducedneurologic diseases : 3024 ~ 7
/ 1995 / A central role for interleukin-1βin the in vitro and in vivo regulation of hepatic inducible nitricoxide synthase : 4890 ~ 8
/ 1995 / Induction of nitric oxide synthase mRNA expression : 26731 ~ 3
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