期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 297, 期 4, 页码 E965-E973出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00323.2009
关键词
contractile function; diabetes; adenosine 5 '-monophosphate-activated protein kinase
资金
- American Heart Association [0355521Z]
- National Institute on Aging [AG-21324]
- Division of Research Resources [INBRE-P20-RR016474]
Li Q, Li J, Ren J. UCF-101 mitigates streptozotocin-induced cardiomyocyte dysfunction: role of AMPK. Am J Physiol Endocrinol Metab 297: E965-E973, 2009. First published August 18, 2009; doi:10.1152/ajpendo.00323.2009.-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 Thr(172) of catalytic alpha-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.
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