Expression Changes of Mitogen-activated Protein Kinase Phosphatase-1 (MKP-1) in Myocardium of Streptozotocin-Induced Diabetic Rats

Abstract

MAP Kinase Phosphatase-1 (MKP-1) is a dual specific phosphatase selective for MAP kinases, and was believed to implicate in the development of cardiac hypertrophy. However, whether MKP-1 is involved in the pathogenesis of diabetic cardiomyopathy is still unknown. We employed streptozotocin (STZ)-induced diabetic Sprague-Dawley rats to study the alteration of the MKP-1 expressions in the left ventricular myocardium in diabetic and normal groups by immunohistochemistry and real-time quantitative reverse transcription-polymerase chain reaction. The weight, blood sugar and urine sugar were measured before and after model induction in both control and diabetic groups. Changes of heart ultrastructure were analyzed by using transmission electron microscopy. The data of weight, blood sugar and urine sugar indicated no significant difference between the two groups before animal model induction. Eight weeks after the induction of diabetes, the differences between the control and the diabetic groups in weight, blood sugar and urine sugar were significant (P<0.01). When compared with control, diabetic myocardium ultrastructural changes included myofibrillar disarrangements, mitochondria disruption, and increase in nuclear membrane invaginations. A significant decrease of MKP-1 expression was observed in the diabetic rats’ myocardium (P<0.01). Our study provides experimental evidences that hyperglycemia could damage myocardial ultrastructure. Moreover, we provided first evidence that down-regulation of cardioprotective peptide MKP-1, the MAPK pathway negative regulator, in myocardium of streptozotocin-induced diabetic rats, which may contribute to the deterioration of cardiac function and lead to diabetic cardiomyopathy.

Diabetic cardiomyopathy - mitogen-activated protein kinase phosphatase-1 - real-time quantitative reverse transcription-polymerase chain reaction - transmission electron microscopy

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1 Grant support: Natural Science Foundation of Zhejiang Province (No. Y204036)
Health bureau Foundation of Zhejiang Province (No. 2006A083)

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