PMID- 27222268 OWN - NLM STAT- MEDLINE DCOM- 20170306 LR - 20201209 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 38 IP - 1 DP - 2016 Jul TI - Tat-ATOX1 inhibits streptozotocin-induced cell death in pancreatic RINm5F cells and attenuates diabetes in a mouse model. PG - 217-24 LID - 10.3892/ijmm.2016.2599 [doi] AB - 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. FAU - Ahn, Eun Hee AU - Ahn EH AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Kim, Dae Won AU - Kim DW AD - 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. FAU - Shin, Min Jea AU - Shin MJ AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Ryu, Eun Ji AU - Ryu EJ AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Yong, Ji In AU - Yong JI AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Chung, Seok Young AU - Chung SY AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Cha, Hyun Ju AU - Cha HJ AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Kim, Sang Jin AU - Kim SJ AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Choi, Yeon Joo AU - Choi YJ AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Kim, Duk-Soo AU - Kim DS AD - Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Chungnam 31538, Republic of Korea. FAU - Cho, Sung-Woo AU - Cho SW AD - Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. FAU - Lee, Keunwook AU - Lee K AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Cho, Yoon Shin AU - Cho YS AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Kwon, Hyeok Yil AU - Kwon HY AD - Department of Physiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea. FAU - Park, Jinseu AU - Park J AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Eum, Won Sik AU - Eum WS AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. FAU - Choi, Soo Young AU - Choi SY AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea. LA - eng PT - Journal Article DEP - 20160520 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (ATOX1 protein, human) RN - 0 (Copper Transport Proteins) RN - 0 (Metallochaperones) RN - 0 (Molecular Chaperones) RN - 0 (Recombinant Fusion Proteins) RN - 0 (tat Gene Products, Human Immunodeficiency Virus) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Cell Death/drug effects MH - Cell Line, Tumor MH - Copper Transport Proteins MH - Diabetes Mellitus, Experimental/*drug therapy/enzymology/pathology MH - Disease Models, Animal MH - Humans MH - Male MH - Metallochaperones/*therapeutic use MH - Mice, Inbred ICR MH - Mitogen-Activated Protein Kinases/metabolism MH - Molecular Chaperones MH - Pancreas/*pathology MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Recombinant Fusion Proteins/isolation & purification/metabolism/pharmacology/*therapeutic use MH - Transduction, Genetic MH - tat Gene Products, Human Immunodeficiency Virus/pharmacology/*therapeutic use EDAT- 2016/05/26 06:00 MHDA- 2017/03/07 06:00 CRDT- 2016/05/26 06:00 PHST- 2015/05/06 00:00 [received] PHST- 2016/04/27 00:00 [accepted] PHST- 2016/05/26 06:00 [entrez] PHST- 2016/05/26 06:00 [pubmed] PHST- 2017/03/07 06:00 [medline] AID - 10.3892/ijmm.2016.2599 [doi] PST - ppublish SO - Int J Mol Med. 2016 Jul;38(1):217-24. doi: 10.3892/ijmm.2016.2599. Epub 2016 May 20.