Tat-ATOX1 inhibits streptozotocin-induced cell death in pancreatic RINm5F cells and attenuates diabetes in a mouse model.

Abstract

Antioxidant1(ATOX1) functions as an antioxidant against hydrogen peroxide and superoxide, and therefore may play a significant role in many human diseases, including diabetes mellitus(DM). In the present study, we examined the protective effects of Tat-ATOX1 protein on streptozotocin(STZ)-exposed pancreatic insulinoma cells (RINm5F) and in a mouse model of STZ-induced diabetes using western blot analysis, immunofluorescence staining and MTT assay, as well as histological and biochemical analysis. Purified Tat-ATOX1 protein was efficiently transduced into RINm5F cells in a dose- and time-dependent manner. Additionally, Tat-ATOX1 protein markedly inhibited reactive oxygen species(ROS) production, DNA damage and the activation of Akt and mitogen activated protein kinases(MAPKs) in STZ-exposed RINm5F cells. In addition, Tat-ATOX1 protein transduced into mice pancreatic tissues and significantly decreased blood glucose and hemoglobinA1c(HbA1c) levels as well as the body weight changes in a model of STZ-induced diabetes. These results indicate that transduced Tat-ATOX1 protein protects pancreatic β-cells by inhibiting STZ-induced cellular toxicityinvitro andinvivo. Based on these findings, we suggest that Tat-ATOX1 protein has potential applications as a therapeutic agent for oxidative stress-induced diseases including DM.