کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5975278 1576216 2013 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Increase in cardiac M2-muscarinic receptor expression is regulated by GATA binding protein 4 (GATA-4) in streptozotocin-induced diabetic rats
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Increase in cardiac M2-muscarinic receptor expression is regulated by GATA binding protein 4 (GATA-4) in streptozotocin-induced diabetic rats
چکیده انگلیسی

BackgroundAn increase in cardiac M2-muscarinic receptor (M2-mAChR) expression in diabetic rats has been observed, but the molecular mechanism of this increase remains unclear. The transcriptional activity of GATA binding protein 4 (GATA-4) has been documented to regulate the expression of M2-mAChR genes. In this study, we were interested in identifying the role of GATA-4 in the increase in M2-mAChR in diabetic rats and a primary culture of cardiomyocytes.MethodsStreptozotocin-induced diabetic rats (STZ-rats) and high-glucose (D-glucose 30 mM, 24 h)-treated primary cultures of cardiomyocytes from neonatal rats were used to investigate the role of GATA-4 in the change in M2-mAChR. The protein expression was determined by Western blot analysis. Phlorizin (Na+-glucose co-transport inhibitor), insulin, tiron (radical scavenger), PD98059 (ERK inhibitor) and SB203580 (p38 inhibitor) were used. We also silenced GATA-4 by RNAi to investigate the changes in M2-mAChR expression.ResultsThe cardiac output was reduced in STZ-rats with a higher expression of M2-mAChR or phosphorylated GATA-4 in the heart. These changes were reversed after correction of the blood sugar level. In cardiomyocytes, high glucose treatment also increased M2-mAChR expression and GATA-4 phosphorylation. These changes were reversed by tiron (ROS scavenger) or PD98059 (MEK/ERK inhibitor). However, an increase in M2-mAChR expression was not observed when GATA-4 was silenced by small interfering RNA (siRNA) in cardiomyocytes.ConclusionsWe suggest that hyperglycemia can cause a higher expression of M2-mAChR in cardiomyocytes mainly through ROS to enhance MEK/ERK for phosphorylation of GATA-4.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Cardiology - Volume 167, Issue 2, 31 July 2013, Pages 436-441
نویسندگان
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