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Glycogen synthase kinase‐3beta suppresses tumor necrosis factor‐alpha expression in cardiomyocytes during lipopolysaccharide stimulation
Author(s) -
Shen E.,
Fan Jue,
Peng Tianqing
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21629
Subject(s) - gsk 3 , gsk3b , tumor necrosis factor alpha , glycogen synthase , protein kinase b , lipopolysaccharide , stimulation , signal transduction , kinase , phosphorylation , biology , chemistry , microbiology and biotechnology , endocrinology
Abstract This study was to investigate the role of glycogen synthase kinase‐3beta (GSK‐3β) in cardiomyocyte tumor necrosis factor‐alpha (TNF‐α) expression induced by lipopolysaccharide (LPS). In cultured neonatal mouse cardiomyocytes, LPS induced TNF‐α expression and increased GSK‐3β activation. Inhibition of GSK‐3β by SB216763 or by over‐expression of a dominant negative mutant of GSK‐3β significantly enhanced TNF‐α expression in LPS‐stimulated cardiomyocytes, in association with an increase in p65 phosphorylation. In contrast, over‐expression of GSK‐3β by adenoviral vectors containing wild‐type GSK‐3β or a constitutively active GSK‐3β attenuated TNF‐α expression induced by LPS. Further evidence to support the inhibitory role of GSK‐3β in TNF‐α expression is that protein kinase B (Akt) signaling, an upstream inhibitor of GSK‐3β, promotes TNF‐α expression in LPS‐stimulated cardiomyocytes and this action of Akt signaling can be mimicked by GSK‐3β inactivation. Our study demonstrates that GSK‐3β plays an inhibitory role in cardiomyocyte TNF‐α expression during LPS stimulation, and it may be a potential therapeutic target for sepsis. J. Cell. Biochem. 104: 329–338, 2008. © 2007 Wiley‐Liss, Inc.