UCF-101 mitigates streptozotocin-induced cardiomyocyte dysfunction: role of AMPK
| العنوان: | UCF-101 mitigates streptozotocin-induced cardiomyocyte dysfunction: role of AMPK |
|---|---|
| المؤلفون: | Qun Li, Jun Ren, Ji Li |
| المصدر: | Am J Physiol Endocrinol Metab |
| بيانات النشر: | American Physiological Society, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Blood Glucose, Male, medicine.medical_specialty, endocrine system diseases, Physiology, Endocrinology, Diabetes and Metabolism, Blotting, Western, Caspase 3, Cell Separation, Pyrimidinones, Diabetic angiopathy, Biology, Resveratrol, Antioxidants, Diabetes Mellitus, Experimental, Mice, chemistry.chemical_compound, Physiology (medical), Internal medicine, Diabetes mellitus, Stilbenes, medicine, Animals, Myocyte, Myocytes, Cardiac, Protease Inhibitors, Protein Phosphatase 2, Phosphorylation, Adenylate Kinase, Thiones, AMPK, Articles, Streptozotocin, medicine.disease, Myocardial Contraction, Retraction, XIAP, Isoenzymes, Mice, Inbred C57BL, Endocrinology, chemistry, Diabetic Angiopathies, medicine.drug |
| الوصف: | Diabetic heart disease contributes to the high mortality in diabetics, although effective clinical management is lacking. The protease inhibitor 5-[5-(2-nitrophenyl) furfuryliodine]-1,3-diphenyl-2-thiobarbituric acid (UCF-101) was reported to protect the hearts against ischemic injury. This study examined the role of UCF-101 on streptozotocin (STZ)-induced diabetic heart defect. Vehicle or UCF-101 was administrated to STZ diabetic mice, and cardiomyocyte mechanical properties were analyzed. UCF-101 reduced STZ-induced hyperglycemia and alleviated STZ-induced aberration in cardiomyocyte contractile mechanics. Diabetes dramatically decreased AMPK phosphorylation at Thr172 of catalytic α-subunit, which was restored by UCF-101. Neither diabetes nor UCF-101 affected the expression of HtrA2/Omi and XIAP or caspase-3 activity. The AMPK activator resveratrol mimicked the UCF-101-induced beneficial effect against diabetic cardiac dysfunction. Mechanical properties in cardiomyocytes from the AMPK-kinase-dead (KD) mice displayed markedly impaired contractile function reminiscent of diabetes. STZ injection in AMPK-KD mice failed to elicit any additional cardiomyocyte contractile defect. UCF-101 significantly downregulated the AMPK-degrading enzymes PP2A and PP2C, the effect of which was mimicked by resveratrol. Taken together, these results indicate that UCF-101 protects against STZ-induced cardiac dysfunction, possibly through AMPK signaling. |
| تدمد: | 1522-1555 0193-1849 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b541ae7b5e32b621f3ddf67b635ee0b4 https://doi.org/10.1152/ajpendo.00323.2009 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b541ae7b5e32b621f3ddf67b635ee0b4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221555 01931849 |
|---|