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Increased PTEN mRNA Expression And Phosphorylation In The Myocardium Of Streptozotocin‐Induced Diabetic Rats: Effects of N‐Acetylcysteine
Author(s) -
Xia Zhengyuan,
Liu Min,
McNeill John H
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.21.5.a435-c
Subject(s) - pten , tensin , pi3k/akt/mtor pathway , protein kinase b , endocrinology , medicine , phosphatase , downregulation and upregulation , streptozotocin , phosphorylation , insulin resistance , chemistry , biology , insulin , diabetes mellitus , signal transduction , microbiology and biotechnology , biochemistry , gene
PTEN (phosphatase and tensin homologue deleted on chromosome ten) negatively regulates cell survival mediated by the phosphatidylinositol 3‐kinase (PI3K)‐Akt pathway. Recently, PTEN has been described as a critical negative regulator in insulin signaling, potentially involved in insulin resistance, Type 2 diabetes and related cardiac complications. High glucose has been shown to downregulate PTEN expression ( Diabetes 2006; 55 :‐2125), possibly through reactive oxygen species‐mediated inactivation of PTEN. We, therefore, hypothesized that PTEN will be downregulated in the myocardium of Type 1 diabetic rats which may contribute to the development of myocardial hypertrophy ( FASEB J 2005; 19 :). Control and streptozotozin‐induced diabetic rats were treated (CT, DT) or untreated (C, D) with antioxidant N‐acetylcysteine (NAC) in the drinking water for 8 weeks. Myocardial total PTEN protein was decreased by about 70% in D rats, accompanied by 2.4‐fold increase of the PI3K p85 protein compared to C. PI3K p85 protein was significantly reduced in DT rats, while total PTEN protein was unchanged compared to D. However, real‐time PCR identified a significant increase of PTEN mRNA in D rat hearts compared to C, which was prevented by NAC. Further study revealed that PTEN protein expression was decreased in the cytosol, but not in the membrane fraction in D rat hearts relative to C hearts, suggestive of increased membrane translocation. Increased PTEN phosphorylation in the myocardial membrane fraction in D rats was normalized by NAC. Contrary to our hypothesis, the results show that PTEN mRNA is upregulated and activated in the myocardium of Type 1 diabetic rats, which might be followed by accelerated degradation.