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Glycogen synthase kinase 3β together with 14‐3‐3 protein regulates diabetic cardiomyopathy: Effect of losartan and tempol
Author(s) -
Gurusamy Narasimman,
Watanabe Kenichi,
Ma Meilei,
Prakash Paras,
Hirabayashi Kenichi,
Zhang Shaosong,
Muslin Anthony J.,
Kodama Makoto,
Aizawa Yoshifusa
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.02.056
Subject(s) - diabetic cardiomyopathy , gsk 3 , glycogen synthase , protein kinase b , gsk3b , medicine , endocrinology , protein kinase a , kinase , losartan , chemistry , phosphorylation , p38 mitogen activated protein kinases , streptozotocin , glycogen , cardiomyopathy , angiotensin ii , receptor , biochemistry , diabetes mellitus , heart failure
Glycogen synthase kinase (GSK) 3β is a multifunctional protein that positively regulates myocardial apoptosis and negatively regulates hypertrophy. However, the role of GSK3β in the diabetic myocardium is largely unknown. We found that GSK3β became more active (less phosphorylated at serine 9) via decreased Akt phosphorylation, in parallel to c‐Jun NH 2 terminal kinase activation, which correlated with increased activated caspase 3 and myocardial apoptosis 3 days after streptozotocin (STZ) injection in mice. However, 28 days after STZ injection, GSK3β became inactive, which correlated with the enhanced protein kinase C β2 and p38 mitogen activated protein kinase expression, nuclear translocation of nuclear factor of activated T cells c3, cardiac hypertrophy and fibrosis. All of the above parameters were exacerbated in dominant‐negative 14‐3‐3 transgenic mice. Our results suggest that GSK3β together with 14‐3‐3 protein plays essential roles in the signaling of diabetic cardiomyopathy, and treatment with either losartan or tempol prevents these changes.