Inhibition of GSK-3beta decreases NF-kappaB-dependent gene expression and impairs the rat liver regeneration.

Abstract:

:Serine-threonine protein kinase glycogen synthase kinase (GSK)-3 is involved in regulation of many cell functions, but its role in regulating liver regeneration is unknown. Here we investigated the effects of GSK-3beta inhibition on liver regeneration after partial hepatectomy in the rat. The potent and selective GSK-3beta inhibitor SB216763 (0.6 mg/kg intravenously) or vehicle (10% dimethyl sulfoxide) was administered 30 min before 70% partial hepatectomy. Liver regeneration was estimated by the cell proliferation, apoptosis, and the related cell signaling and cycling proteins. In 30 min after hepatectomy in the rat, GSK-3beta was found to be translocated to the nucleus, but GSK-3beta inhibitor SB216763 that could phosphorylate residue Ser9 on GSK-3beta did not attenuated the accumulation. Consequently, the inhibition of GSK-3beta decreased the nuclear factor-kappaB activity, the NF-kappaB-dependent gene expression, and COX2 expression, but enhanced p21(WAF1/Cip1) transcription. Moreover, the injection of SB216763 impaired the proliferation cell nuclear antigen (PCNA) index and increased the apoptosis of liver compared to the vehicle. GSK-3beta plays an important role in rat liver regeneration. We conclude it may partially result from the inhibition of the NF-kappaB pathway and enhancement of p21 (WAF1/Cip1) expression.

journal_name

J Cell Biochem

authors

Chen H,Yang S,Yang Z,Ma L,Jiang D,Mao J,Jiao B,Cai Z

doi

10.1002/jcb.21358

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

1281-9

issue

5

eissn

0730-2312

issn

1097-4644

journal_volume

102

pub_type

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