Uncoupling protein 2 regulates myocardial apoptosis via the diabetogenic action of streptozotocin
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Abstract
Objective: Determine the role of uncoupling protein 2 (UCP2) in the myocardial apoptosis of diabetic mellitus(DM). Methods: DM animal models were induced by streptozotocinon (STZ) on UCP2 knock-out mice (UCP2KO) and wild-type mice (WT), which were reared for 7 and 28 days after successful modeling, respectively. The expressions of relative protein for myocardial apoptosis, pro-caspase-9, were investigated using western blot. However, the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) was used to explain apoptosis at the DNA level. Results: Image analysis showed that the expression of pro-caspase-9 protein levels increased slightly in UCP-/- + DM-7-day group comparing with DM-7-day group (P > 0.05). The expression of pro-caspase-9 protein levels increased significantly (P < 0.05)in UCP-/- + DM-28-day group comparing with DM-28-day group. TUNEL analysis indicated that UCP2 reduced the number of apoptotic myocytes in the DM-28-day group by 70% in comparison to DM-7-day group by 30% (P < 0.05). Conclusion UCP2 may be one of the most important factors that contribute to the myocardial apoptosis of DM.
- Ricquier, D. and Bouillaud, F. (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochemical Journal, 345, 161-179. doi:10.1042/0264-6021:3450161
- Blanc, J., Alves-Guerra, M.C., Esposito, B., et al. (2003) Protective role of uncoupling protein 2 in atherosclerosis. Circulation, 107, 388-390. doi:10.1161/01.CIR.0000051722.66074.60
- Chan, C.B., Saleh, M.C., Koshkin, V., et al. (2004) Uncoupling protein 2 and islet function. Diabetes, 53, 136-142. doi:10.2337/diabetes.53.2007.S136
- Arsenijevic, D., Onuma, H., Pecqueur, C., et al. (2000) Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nature Genetics, 26, 435-439. doi:10.1038/82565
- Teshima, Y., Akao, M., Jones, S.P., et al. (2003) Uncoupling protein-2 overexpression inhibits mitochondrial death pathway in cardiomyocytes circulation research. Circulation Research, 93, 192-200。 doi:10.1161/01.RES.0000085581.60197.4D
- Brand, M.D., Buckingham, J.A., Esteves, T.C., et al. (2004) Mitochondrial superoxide and aging: Uncoupling-protein activity and superoxide production. Biochemical Society Symposia, 71, 203-213.
- Zhang, C., Baffy, G., Perret, P., et al. (2001) Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, β-cell dysfunction, and type2 diabetes. Cell, 105, 745-755. doi:10.1016/S0092-8674(01)00378-6
- King, L.M., Sidell, R.J., Wilding, J.R., Radda, G.K. and Clarke, K. (2001) Free fatty acids, but not ketone bodies, protect diabetic rat hearts during low-?ow ischemia. American Journal of Physiology—Heart and Circulatory Physiology, 280, H1173-H1181.
- Li, Z.H., Zhang, T., Dai, H.Y., et al. (2007) Involvement of endoplasmic reticulum stress in myocardial apoptosis of streptozocin-induced diabetic rats. Journal of Clinical Biochemistry and Nutrition, 41, 58-67. doi:10.3164/jcbn.2007008
- Devereux, R.B., Roman, M.J., Paranicas, M., et al. (2000) Impact of diabetes on cardiac structure and function: The strong heart study. Circulation, 101, 2271-2276.
- Rubler, S., Dlugash, J., Yuceoglu, Y.Z., et al. (1997) New type of cardiomyopathy associated with diabetic Glomerulosclerosis. American Journal of Cardiology, 30, 595-602.
- doi:10.1016/0002-9149(72)90595-4
- Wei, X.X., Zhou, X.P., He, D., et al. (1992) Cardiac disease in streptozocin-induced diabetes. Chinese Journal of Endocrinology and Metabolism, 4, 222-225.