title: Tat-ATOX1 inhibits streptozotocin-induced cell death in pancreatic RINm5F cells and attenuates diabetes in a mouse model.
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.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Ahn
authors.affiliation: 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.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Min Jea
authors.initials: MJ
authors.lastname: Shin
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Ryu
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Ji In
authors.initials: JI
authors.lastname: Yong
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Seok Young
authors.initials: SY
authors.lastname: Chung
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Chungnam 31538, Republic of Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Keunwook
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Yoon Shin
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea.
authors.forename: Hyeok Yil
authors.initials: HY
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon‑do 24252, Republic of Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D000079922:Copper Transport Proteins; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D056511:Metallochaperones / Q000627:therapeutic use*; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018832:Molecular Chaperones; D010179:Pancreas / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D014161:Transduction, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C474500:ATOX1 protein, human; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases