Hepatic Ischemia/Reperfusion in Rats Induces iNOS Gene Transcription by Activation of NF-κB

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Title
Hepatic Ischemia/Reperfusion in Rats Induces iNOS Gene Transcription by Activation of NF-κB
Author(s)
Gang Min Hur; Young Sue Ryu; Hyo Yung Yun; Byeong Hwa Jeon; Yong Man Kim; Jeong Ho Seok; Jae Heun Lee
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 261, no. 3, pp. 917-922
Publication Year
1999
Abstract
It has been known that many immediately early genes are expressed during ischemia/reperfusion (I/R) injury. Here, employing a model of hepatic I/R, we show that inducible nitric oxide synthase (iNOS) is induced via the activation of nuclear factor kappaB (NF-κB) after I/R in rat liver. When liver was subjected to ischemia followed by reperfusion, but not ischemia alone, an NF-κB complex composed of p50/p65 heterodimer and p50 homodimer was rapidly activated within 1 h and remained elevated for up to 3 h, and then tended to decline after 5 h of reperfusion. Also, the expression of iNOS mRNA was initiated after 1 h and continued to increase after 5 h of reperfusion during the time course studied. This upregulated iNOS mRNA expression coincides with increased iNOS enzyme activity and NF-κB binding activity after hepatic I/R. Administration of N-acetylcysteine (NAC, 20 mg/kg i.v. 10 min before reperfusion), an antioxidant, not only significantly inhibited the expression of iNOS mRNA but also blocked upregulated NF-κB binding activity after reperfused liver. These results suggest that NF-κB is activated by oxidative stress during hepatic I/R and may play a significant role in the induction of the iNOS gene.
ISSN
0006-291X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1006/bbrc.1999.1143
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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