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UCF- 101 mitigates streptozotocin-induced cardiomyocyte dysfunction: role of AMPK.
- Source :
- American Journal of Physiology: Endocrinology & Metabolism; Oct2009, Vol. 297, pE965-E973, 9p
- Publication Year :
- 2009
-
Abstract
- 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 UCF101 on streptozotocin (STZ)-induced diabetic heart defect. Vehicle or UCF101 was administrated to STZ diabetic mice, and cardiomyocyte mechanical properties were analyzed. UCF101 reduced STZ-induced hyperglycemia and alleviated STZ-induced aberration in cardiomyocyte contractile mechanics. Diabetes dramatically decreased AMPK phosphorylation at Thr<superscript>172</superscript> of catalytic α-subunit, which was restored by UCF101. 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 (1(D) mice displayed markedly impaired contractile function reminiscent of diabetes. STZ injection in AMPK-KD mice failed to elicit any additional cardiomyocyte contractile defect. UCF101 significantly downregulated the AMPK-degrading enzymes PP2A and PP2C, the effect of which was mimicked by resveratrol. Taken together, these results indicate that UCF101 protects against STZ-induced cardiac dysfunction, possibly through AMPK signaling. [ABSTRACT FROM AUTHOR]
- Subjects :
- HEART cells
PROTEIN kinases
DIABETES
ADENOSINES
STREPTOZOTOCIN
Subjects
Details
- Language :
- English
- ISSN :
- 01931849
- Volume :
- 297
- Database :
- Complementary Index
- Journal :
- American Journal of Physiology: Endocrinology & Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 44657575
- Full Text :
- https://doi.org/10.1152/ajpendo.00323.2009