کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10954463 | 1097906 | 2005 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Adenosine triggers preconditioning through MEK/ERK1/2 signalling pathway during hypoxia/reoxygenation in neonatal rat cardiomyocytes
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کلمات کلیدی
extracellular signal regulated kinase 1/2Adenosine A1 receptor - آدنوزین A1 گیرندهAdenosine A3 receptor - آدنوزین A3 گیرندهReoxygenation - اکسیداسیونApoptosis - خزان یاختهایPhosphatidylinositol 3-kinase - فسفاتیدیلینواستیل 3-کینازCardiomyocytes - قلب و عروقlactate dehydrogenase - لاکتات دهیدروژناز Hypoxia - هیپوکسیprotein kinase B - پروتئین کیناز Bcaspase 3 - کاسپاز 3Adenosine A2A receptor - گیرنده آدنوزین A2A
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Three subtypes of adenosine receptors (A1, A2A and A3 ARs) are functionally expressed in cardiomyocytes. Adenosine released during ischemia and ischemia/reperfusion plays a major role in cardioprotection. Phosphatidylinositol 3-kinase (PI-3K)/protein kinase B (PKB) and MEK/ERK1/2 pathways are involved in cell survival. Since the role of these pathways in AR-mediated preconditioning is poorly understood, we have investigated whether PI-3K/PKB and/or MEK1/ERK1/2 pathways are involved in AR-induced cardioprotection in neonatal rat cardiomyocytes. Cells were pre-treated (15Â min) with adenosine (non-selective), CPA (A1), CGS 21680 (A2A) or Cl-IB-MECA (A3) before 4Â h hypoxia (0.5% O2) and 18Â h reoxygenation (HX4/R). HX4/R-induced increase in LDH release was significantly reduced by adenosine (70%), CPA (59%) and Cl-IB-MECA (46%). The MEK1 inhibitor PD 98059 suppressed the effects of adenosine, CPA, and Cl-IB-MECA on LDH release, whereas the PI-3K inhibitor wortmannin did not reverse this cardioprotection. Western blotting of phosphorylated ERK1/2 and PKB during HX4/R supported the involvement of ERK1/2 and not PKB in A1 and A3 agonist-mediated cardioprotection. In addition, adenosine, CPA and Cl-IB-MECA inhibited HX4/R-induced caspase 3 activity by 75%, 70% and 59%, respectively, and this inhibition was abolished by PD 98059. Interestingly, wortmannin inhibited by 66% the anti-apoptotic response triggered by Cl-IB-MECA but had no effect on adenosine or CPA-induced inhibition of caspase 3. CGS 21680 did not modify cell survival or caspase 3 activity. In conclusion, these data show that the preconditioning effect of adenosine requires A1 and A3 but not A2A ARs and involves an anti-apoptotic effect via MEK1/ERK1/2 pathway in neonatal rat cardiomyocytes. In addition, A3AR-induced preconditioning also involves a PI-3K dependent pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 39, Issue 3, September 2005, Pages 429-442
Journal: Journal of Molecular and Cellular Cardiology - Volume 39, Issue 3, September 2005, Pages 429-442
نویسندگان
R. Germack, J.M. Dickenson,