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Activation of glycogen synthase kinase 3β participates in hypoxia‐induced cardiomyocyte apoptosis
Author(s) -
Zhou Zhou,
Chen Alex F.
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.a1288-d
Subject(s) - apoptosis , hypoxia (environmental) , gsk 3 , viability assay , western blot , glycogen synthase , signal transduction , biology , microbiology and biotechnology , myocyte , phosphorylation , kinase , caspase 3 , caspase , chemistry , endocrinology , medicine , programmed cell death , biochemistry , gene , organic chemistry , oxygen
Background: Hypoxia is a vital initiating factor in myocardial dysfunction, and apoptosis of myocytes contributes to hypoxia‐induced heart failure. Glycogen synthase kinase 3β (GSK3β) has recently been identified as a key intermediate in several apoptotic signaling pathways. This study tested the hypothesis that GSK‐3β activation results in hypoxia‐induced cardiomyocyte apoptosis. Methods: Primary cultured neonatal ventricular myocytes from normal Wister rats (3d) were used. Cell apoptosis and viability were determined by Hoechst 33342 nuclear staining and MTT absorbance at 0, 3, 6, 12, 24 h after hypoxia, respectively. Expressions of GSK3β, caspases−9, −3 mRNA and phosphorylation of GSK3β protein were measured by RT‐PCR and Western blot, respectively. Changes of caspase‐9 enzymes activity were assessed by a colorimetric assay with the use of specific substrates. Results: Typical cell apoptosis was observed in cardiomyocytes and cell viability was significantly decreased 24 h after hypoxia. GSK3β mRNA and Caspase‐9 mRNA expressions were increased 3–24 h after hypoxia, whereas caspase‐3 mRNA expression was increased 12, 24 h after hypoxia. The phosphorylated form of GSK3β was increased 6‐24 h after hypoxia, whereas caspase‐9 activity was markedly elevated 3–24 h after hypoxia. Conclusion: Activation of GSK3β signal transduction pathway participates in hypoxia‐induced cardiomyocytes apoptosis.