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学科主题基础医学
mPGES-2 deletion remarkably enhances liver injury in streptozotocin-treated mice via induction of GLUT2
Sun, Ying1,2,3; Jia, Zhanjun1,2; Yang, Guangrui1,2; Kakizoe, Yutaka1,2; Liu, Mi1,2,4; Yang, Kevin T.1,2,4; Liu, Ying1,2; Yang, Baoxue3; Yang, Tianxin1,2,4
关键词Mpges-2 Glucose Transporter 2 Streptozotocin Diabetes Prostaglandin E-2
刊名JOURNAL OF HEPATOLOGY
2014-12-01
61期:6页:1328-1336
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Gastroenterology & Hepatology
研究领域[WOS]Gastroenterology & Hepatology
关键词[WOS]PROSTAGLANDIN-E SYNTHASE ; POLY(ADP-RIBOSE) POLYMERASE GENE ; PTGES2 ARG298HIS POLYMORPHISM ; GLUCOSE-TRANSPORTER ; IN-VIVO ; PANCREATIC-ISLETS ; DNA-DAMAGE ; CELLS ; ASSOCIATION ; EXPRESSION
英文摘要

Background & Aims: Microsomal prostaglandin E synthase-2 (mPGES-2) deletion does not influence in vivo PGE(2) production and the function of this enzyme remains elusive. The present study was undertaken to investigate the role of mPGES-2 in streptozotocin (STZ)-induced type-1 diabetes and organ injuries.

Methods: mPGES-2 wild type (WT) and knockout (KO) mice were treated by a single intraperitoneal injection of STZ at the dose of 120 mg/kg to induce type-1 diabetes. Subsequently, glycemic status and organ injuries were evaluated.

Results: Following 4 days of STZ administration, mPGES-2 KO mice exhibited severe lethality in contrast to the normal phenotype observed in WT control mice. In a separate experiment, the analysis was performed at day 3 of the STZ treatment in order to avoid lethality. Blood glucose levels were similar between STZ-treated KO and WT mice. However, the livers of KO mice were yellowish with severe global hepatic steatosis, in parallel with markedly elevated liver enzymes and remarkable stomach expansion. However, the morphology of the other organs was largely normal. The STZ-treated KO mice displayed extensive hepatocyte apoptosis compared with WT mice in parallel with markedly enhanced inflammation and oxidative stress. More interestingly, a liver-specific 50% upregulation of GLUT2 was found in the KO mice accompanied with a markedly enhanced STZ accumulation and this induction of GLUT2 was likely to be associated with the insulin/SREBP-1c pathway. Primary cultured hepatocytes of KO mice exhibited an increased sensitivity to STZ-induced injury and higher cellular STZ content, which was markedly blunted by the selective GLUT2 inhibitor phloretin.

Conclusions: mPGES-2 deletion enhanced STZ-induced liver toxicity possibly via GLUT2-mediated STZ uptake, independently of diabetes mellitus. (C) 2014 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.

语种英语
WOS记录号WOS:000345115600020
项目编号DK094956 ; 31330037 ; 2012CB517600 ; 2012CB517602 ; 11SDG7480006
资助机构National Institutes of Health ; National Natural Science Foundation of China ; National Basic Research Program of China 973 Program ; American Heart Association
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51790
专题北京大学基础医学院_药理学系
北京大学基础医学院
北京大学临床肿瘤学院_VIP-Ⅱ
作者单位1.Vet Affairs Med Ctr, Salt Lake City, UT 84132 USA
2.Univ Utah, Dept Internal Med, Salt Lake City, UT 84132 USA
3.Peking Univ, Dept Pharmacol, Sch Basic Med Sci, Beijing 100871, Peoples R China
4.Sun Yat Sen Univ, Sch Med, Inst Hypertens, Guangzhou 510275, Guangdong, Peoples R China
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GB/T 7714
Sun, Ying,Jia, Zhanjun,Yang, Guangrui,et al. mPGES-2 deletion remarkably enhances liver injury in streptozotocin-treated mice via induction of GLUT2[J]. JOURNAL OF HEPATOLOGY,2014,61(6):1328-1336.
APA Sun, Ying.,Jia, Zhanjun.,Yang, Guangrui.,Kakizoe, Yutaka.,Liu, Mi.,...&Yang, Tianxin.(2014).mPGES-2 deletion remarkably enhances liver injury in streptozotocin-treated mice via induction of GLUT2.JOURNAL OF HEPATOLOGY,61(6),1328-1336.
MLA Sun, Ying,et al."mPGES-2 deletion remarkably enhances liver injury in streptozotocin-treated mice via induction of GLUT2".JOURNAL OF HEPATOLOGY 61.6(2014):1328-1336.
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