Tat-ATOX1 inhibits streptozotocin-induced cell death in pancreatic RINm5F cells and attenuates diabetes in a mouse model
- Authors
- 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
- Issue Date
- Jul-2016
- Publisher
- Demetrios A. Spandidos Ed. & Pub.
- Keywords
- Tat-antioxidant 1; diabetes mellitus; blood glucose; hemoglobin A1c; oxidative stress; protein therapy
- Citation
- International Journal of Molecular Medicine, v.38, no.1, pp 217 - 224
- Pages
- 8
- Journal Title
- International Journal of Molecular Medicine
- Volume
- 38
- Number
- 1
- Start Page
- 217
- End Page
- 224
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/8970
- DOI
- 10.3892/ijmm.2016.2599
- ISSN
- 1107-3756
1791-244X
- 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 beta-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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Collections - College of Medicine > Department of Anatomy > 1. Journal Articles
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