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Pituitary adenylate cyclase‐activating polypeptide attenuates streptozotocin‐induced apoptotic death of RIN‐m5F cells through regulation of Bcl‐2 family protein mRNA expression
Author(s) -
Onoue Satomi,
Hanato Junko,
Yamada Shizuo
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06672.x
Subject(s) - streptozotocin , apoptosis , programmed cell death , lactate dehydrogenase , biology , endocrinology , adenylate kinase , medicine , chemistry , microbiology and biotechnology , biochemistry , enzyme , diabetes mellitus
Oxidative stress, followed by the apoptotic death of pancreatic β cells, is considered to be one of causative agents in the evolution of the type 2 diabetic state; therefore, the protection of β cells can comprise an efficacious strategy for preventing type 2 diabetes. In the present study, RIN‐m5F cells (i.e. the rat insulinoma β 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 m m , as demonstrated by terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling staining and 2.6‐fold activation of cellular caspase‐3, an apoptotic enzyme. By contrast, some neuropeptides of the glucagon‐secretin family and coenzyme Q 10 , an endogenous mitochondrial antioxidant, could attenuate streptozotocin 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 PACAP on streptozotocin‐evoked up‐regulation of pro‐apoptotic factor (Noxa and Bax) and a 2.3‐fold enhancement of Bcl‐2 mRNA expression, a pro‐survival protein, was also observed after addition of PACAP. The data obtained suggest the anti‐apoptotic role of PACAP in streptozotocin‐treated RIN‐m5F cells through the regulation of pro‐apoptotic and pro‐survival factors.