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KMID : 0378120020290010053
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Chungnam Medical Journal
2002 Volume.29 No. 1 p.53 ~ p.69
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Transcriptional Control of Inducible Nitric Oxide Synthase by NF-kB in Regenerating Rat Liver
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Hur Gang-Min
Ryu Young-Sue
Bea So-Hyun
Hong Jang-Hee
Lee Jea-Heun
Seok Jeong-Ho
Kim Joon-Young
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Abstract
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A concerted activation of transcription factors and inducible nitric oxide synthase (iNOS) gene expression by the transcription factors were observed after partial hepatectomy (PH) of rats. To define the molecular mechanism of transcriptional control of iNOS gene during the hepatic regeneration, expression of iNOS, interleukin-6 (IL-6) and tumor necrosis-alpha (TNF-α) mRNA and the binding pattern of nuclear transcriptional factor (NF-κB and STAT-3) in the iNOS gene promoter region have been investigated.
The expression of iNOS mRNA was initiated at 1 h post-PH and reached a maximum at 3 h and 5 h post-PH. This induction was preceded by an early and transient activation of NF- KB complex composed of p50/p65 heterodimer, which was rapidly activated within 30 min post-PH and remained elevated for up to 1 h post-PH, and tend to decline after 3 h post-PH. Administration of N-acetylcysteine (NAC) significantly inhibited the expression of iNOS mRNA.
Expression of IL-6 and TNF-α, activators of iNOS and STAT-3, were also increased after PH, but the activation of STAT-3 binding during hepatic regeneration was found at 3 h or 5 h post-PH, which shows a different time kinetic pattern of transcriptional factor activation of iNOS gene between NF-κB and STAT-3.
These results suggest that there is an important role of the NF-κB complex (p50/p65 heterodimer) activation in the transcriptional control of iNOS gene during hepatic regeneration.
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KEYWORD
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iNOS, NF-kB, Hepatic regenerating cells
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