TAILIEUCHUNG - Báo cáo khoa học: Pituitary adenylate cyclase-activating polypeptide attenuates streptozotocin-induced apoptotic death of RIN-m5F cells through regulation of Bcl-2 family protein mRNA expression

Oxidative stress, followed by the apoptotic death of pancreaticbcells, is considered to be one of causative agents in the evolution of the type 2 dia-betic state; therefore, the protection ofbcells can comprise an efficacious strategy for preventing type 2 diabetes. In the present study, RIN-m5F cells (. the rat insulinoma bcell line) were stimulated with streptozotocin, resulting in a time- and concentration-dependent release of lactate dehydrogenase. | ễFEBS Journal Pituitary adenylate cyclase-activating polypeptide attenuates streptozotocin-induced apoptotic death of RIN-m5F cells through regulation of Bcl-2 family protein mRNA expression Satomi Onoue Junko Hanato and Shizuo Yamada Department of Pharmacokinetics and Pharmacodynamics and GlobalCenter of Excellence Program Schoolof PharmaceuticalSciences University of Shizuoka Japan Keywords apoptosis PACAP RIN-m5F cells streptozotocin Correspondence S. Onoue Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence Program Schoolof PharmaceuticalSciences University of Shizuoka 52-1 Yada Suruga-ku Shizuoka 422-8526 Japan Fax 81 569 74 4748 Tel 81 569 74 4855 E-mail onoue@ Received 21 July 2008 revised 2 September 2008 accepted 8 September 2008 doi Oxidative stress followed by the apoptotic death of pancreatic b cells is considered to be one of causative agents in the evolution of the type 2 diabetic state therefore the protection of b cells can comprise an efficacious strategy for preventing type 2 diabetes. In the present study RIN-m5F cells . the rat insulinoma b cell line were stimulated with streptozotocin resulting in a time- and concentration-dependent release of lactate dehydrogenase. There appeared to be significant apoptotic cell death after 2 h of treatment with streptozotocin at 10 mM as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining and activation of cellular caspase-3 an apoptotic enzyme. By contrast some neuropeptides of the glucagon-secretin family and coenzyme Q10 an endogenous mitochondrial antioxidant could attenuate streptozo-tocin cytotoxicity and especially pituitary adenylate cyclase-activating polypeptide PACAP at a concentration of 10 7 M exhibited 34 attenuation of lactate dehydrogenase release from streptozotocin-treated RIN-m5F cells. Quantitative RT-PCR experiments indicated the inhibitory effect of

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