Premium
Activation of GSK‐3β inhibited TNF‐α expression in cardiomyocytes during LPS stimulation
Author(s) -
Shen E,
Fan Jue,
Peng Tianqing
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1281
Subject(s) - gsk 3 , ly294002 , protein kinase b , gsk3b , tumor necrosis factor alpha , microbiology and biotechnology , chemistry , green fluorescent protein , messenger rna , stimulation , lipopolysaccharide , signal transduction , biology , endocrinology , biochemistry , gene
This study was to investigate the role of glycogen synthase kinase (GSK)‐3β in cardiomyocyte TNF‐α expression induced by lipopolysaccharides (LPS). Neonatal mouse cardiomyocytes were cultured and incubated with LPS in the presence of SB216763, a specific inhibitor of GSK‐3β, or DMSO for 4 hours. SB216763 increased both TNF‐α protein and mRNA expression, suggesting an inhibitory role of GSK‐3β. To substantiate the role of GSK‐3β, cardiomyocytes were infected with recombinant adenoviruses containing GSK‐3β(Ad‐GSK) or dominant active mutant of GSK‐3β (Ad‐AC‐GSK) or dominant negative mutant of GSK‐3β(Ad‐DN‐GSK) or Green Fluorescent Protein (GFP) (Ad‐GFP) for 24 hours, followed by incubation with LPS for 4 hours. Both Ad‐GSK and Ad‐AC‐GSK infection decreased whereas Ad‐DN‐GSK increased TNF‐α protein and mRNA expression, compared to Ad‐GFP. This result supported the inhibitory role of GSK‐3β in TNF‐α expression in LPS‐stimulated cardiomyocytes. In addition, inhibition of protein kinase B activation (AKT) by either LY294002 or over‐expression of dominant negative mutant of AKT significantly decreased TNF‐α protein and mRNA expression in LPS‐stimulated cardiomyocytes. As AKT suppresses GSK‐3β activation, our data further supports the notion that GSK‐3β inhibits TNF‐α expression. In conclusion, our study demonstrated an inhibitory role of GSK‐3β in LPS‐stimulated TNF‐α expression, suggesting that GSK‐3β may be a therapeutic target for sepsis.