Reg2 protects mouse insulinoma cells from streptozotocin-induced mitochondrial disruption and apoptosis

Abstract

We reported previously that pancreas-specific ablation of IGF-I in mice induced an increased expression of regenerating family proteins Reg2 and Reg3β in the pancreas and protected them from streptozotocin (Stz)-induced β-cell damage. We, therefore, assessed the effect of ectopically introduced Reg2 on Stz-induced apoptosis in MIN6 mouse insulinoma cells and report here that Reg2 protects MIN6 cells from Stz-induced apoptosis by attenuating its ability to disrupt mitochondrial membrane integrity, activate caspase-3 and promote poly-ADP ribose polymerase cleavage, and induce apoptosis. These changes correlated with suppression of c-jun N-terminal kinase (JNK) phosphorylation by Stz. Reg2 inhibited Stz-induced proapoptotic events as well as the inactivation of JNK. Inclusion of chemical inhibitor of JNK to Reg2 expressing cells rendered them sensitive to Stz. These data demonstrate that Reg2 protects insulin-producing cells against Stz-induced apoptosis by interfering with its cytotoxic signaling upstream of the intrinsic proapoptotic events by preventing its ability to inactivate JNK.

Keywords::

• Apoptosis
• caspase
• insulinoma cells
• c-Jun N-terminal kinase
• mitochondrial membrane potential

Acknowledgments

This study was supported by grants from the Canadian Institutes of Health Research (NMD-83124 & MOP-84389). JLL is a senior Chercheur Boursier of the Fonds de la Recherché en Santé du Quebec.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.