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

Ahn,Eun  Hee; Kim,Dae  Won; Shin,Min  Jea; Ryu,Eun  Ji; Yong,Ji  In; Chung,Seok  Young; Cha,Hyun  Ju; Kim,Sang  Jin; Choi,Yeon  Joo; Kim,Duk-Soo; Cho,Sung-Woo; Lee,Keunwook; Cho,Yoon  Shin; Kwon,Hyeok  Yil; Park,Jinseu; Eum,Won  Sik; Choi,Soo  Young

doi:10.3892/ijmm.2016.2599

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

Authors:
- Eun Hee Ahn
- Dae Won Kim
- Min Jea Shin
- Eun Ji Ryu
- Ji In Yong
- Seok Young Chung
- Hyun Ju Cha
- Sang Jin Kim
- Yeon Joo Choi
- Duk-Soo Kim
- Sung-Woo Cho
- Keunwook Lee
- Yoon Shin Cho
- Hyeok Yil Kwon
- Jinseu Park
- Won Sik Eum
- Soo Young Choi
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Affiliations: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea, Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, Gangwon-do 25457, Republic of Korea, Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Chungnam 31538, Republic of Korea, Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea, Department of Physiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea
Published online on: May 20, 2016 https://doi.org/10.3892/ijmm.2016.2599
Pages: 217-224

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Abstract

Antioxidant 1 (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 hemoglobin A1c (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 toxicity in vitro and in vivo. Based on these findings, we suggest that Tat-ATOX1 protein has potential applications as a therapeutic agent for oxidative stress-induced diseases including DM.

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