| First Author | Li Q | Year | 2009 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 297 |
| Issue | 4 | Pages | E965-73 |
| PubMed ID | 19690068 | Mgi Jnum | J:159577 |
| Mgi Id | MGI:4443276 | Doi | 10.1152/ajpendo.00323.2009 |
| Citation | Li Q, et al. (2009) UCF-101 mitigates streptozotocin-induced cardiomyocyte dysfunction: role of AMPK. {RETRACTED}. Am J Physiol Endocrinol Metab 297(4):E965-73 |
| abstractText | 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. |
