| Summary: | 碩士 === 國立成功大學 === 藥理學研究所 === 98 === Diabetic cardiomyopathy as diabetes-specific complication refers to a disease process which eventually leads to left ventricular hypertrophy and diastolic and systolic dysfunction. Recent reports have shown that hyperglycemia induces reactive oxygen species (ROS) in cardiomyocytes, which contributes to diabetic cardiomyopathy. In this study, we observed the lower cardiac output in STZ-induced diabetic rats. The expression of cardiac troponin I (cTnI) and level of GATA-4 phosphorylation was increased. This changes could be reversed by insulin or phlorizin pretreatment. We also demonstrated that the condition of hyperglycemia was failed to increased the expression of cTnI, when GATA-4 is absent. Activation of ERK is known as its ability to phosphorylate serine105 of GATA4, and this had been reported to increase the DNA binding activity of this transcription factor. On the other hand, GSK-3β could directly interact with GATA-4 and cause GATA4 exported from nuclear. In current study, ROS production, higher level of cTnI expression and GATA-4 phosphorylation were observed in high glucose (HG)-treated H9c2 cells. GATA-4 nuclear translocalization and GSK-3β ser9 phosphorylation level were elevated in HG treated H9c2 cells. These changes could be reversed in the presence of tiron (ROS scavengers) , PD98059 (MEK/ERK inhibitors), and GATA-4 RNAi. Results of cell contractility assay also indicate that HG decreased contractility of H9c2 cells. Further more, contractilities was not affected by HG in H9c2 cells after GATA-4 knockdown. Taken together, we have demonstrated that hyperglycemia cause systolic dysfunction and elevatd expression of cTnI in cardiomyocytes through GATA-4 phosphorylation.
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