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

被引：16

作者：

Ahn, Eun Hee ^{[1
,2
]}

Kim, Dae Won ^{[3
]}

Shin, Min Jea ^{[1
,2
]}

Ryu, Eun Ji ^{[1
,2
]}

Yong, Ji In ^{[1
,2
]}

Chung, Seok Young ^{[1
,2
,7
]}

Cha, Hyun Ju ^{[1
,2
]}

Kim, Sang Jin ^{[1
,2
]}

Choi, Yeon Joo ^{[1
,2
]}

Kim, Duk-Soo ^{[4
]}

Cho, Sung-Woo ^{[5
]}

Lee, Keunwook ^{[1
,2
]}

Cho, Yoon Shin ^{[1
,2
]}

Kwon, Hyeok Yil ^{[6
]}

Park, Jinseu ^{[1
,2
]}

Eum, Won Sik ^{[1
,2
]}

Choi, Soo Young ^{[1
,2
]}

机构：

[1] Hallym Univ, Dept Biomed Sci, 1 Hallymdaehak Gil, Chunchon 24252, Gangwon Do, South Korea

[2] Hallym Univ, Res Inst Biosci & Biotechnol, 1 Hallymdaehak Gil, Chunchon 24252, Gangwon Do, South Korea

[3] Gangneung Wonju Natl Univ, Coll Dent, Res Inst Oral Sci, Dept Biochem & Mol Biol, Kangnung 25457, Gangwon Do, South Korea

[4] Soonchunhyang Univ, Coll Med, Dept Anat, Cheonan Si 31538, Chungnam, South Korea

[5] Univ Ulsan, Coll Med, Dept Biochem & Mol Biol, Seoul 05505, South Korea

[6] Hallym Univ, Coll Med, Dept Physiol, Chunchon 24252, Gangwon Do, South Korea

[7] Shaker High Sch, Latham, NY 12110 USA

来源：

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2016年 / 38卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Tat-antioxidant; 1; diabetes mellitus; blood glucose; hemoglobin A1c; oxidative stress; protein therapy; NF-KAPPA-B; PROTEIN; TRANSDUCTION; DOMAIN; INJURY; HYPERGLYCEMIA; ANTIOXIDANT; MECHANISM; PATHWAY; DAMAGE;

D O I：

10.3892/ijmm.2016.2599

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

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.

引用

页码：217 / 224

页数：8

共 46 条

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