张华莉

教授 博士生导师 硕士生导师

入职时间:1997-07-09

所在单位:基础医学院

学历:博士研究生毕业

办公地点:湘雅老校区第二教学楼5楼

性别:女

联系方式:15607310187

学位:医学博士学位

在职信息:在职

主要任职:湖南省脓毒症转化医学重点实验室学术委员会副主任,湖南省病理生理学会副理事长,危重病专业委员会副主任委员,中国病理生理学会常务理事

毕业院校:中南大学

学科:基础医学

曾获荣誉:

2013-06-01  当选:  中南大学“升华学者”特聘教授

2013-06-01  当选:  湖南省自然科学杰出青年基金获得者

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Glutathione-dependent reductive stress triggers mitochondrial oxidation and cytotoxicity.

发布时间:2021-06-02

点击次数:

发表刊物:FASEB J .

关键字:redox potential, thioredoxin, roGFPs, reactive oxygen species

摘要:To investigate the effects of the predominant nonprotein thiol, glutathione (GSH), on redox homeostasis, we employed complementary pharmacological and genetic strategies to determine the consequences of both loss- and gain-of-function GSH content in vitro. We monitored the redox events in the cytosol and mitochondria using reduction-oxidation sensitive green fluorescent protein (roGFP) probes and the level of reduced/oxidized thioredoxins (Trxs). Either H(2)O(2) or the Trx reductase inhibitor 1-chloro-2,4-dinitrobenzene (DNCB), in embryonic rat heart (H9c2) cells, evoked 8 or 50 mV more oxidizing glutathione redox potential, E(hc) (GSSG/2GSH), respectively. In contrast, N-acetyl-L-cysteine (NAC) treatment in H9c2 cells, or overexpression of either the glutamate cysteine ligase (GCL) catalytic subunit (GCLC) or GCL modifier subunit (GCLM) in human embryonic kidney 293 T (HEK293T) cells, led to 3- to 4-fold increase of GSH and caused 7 or 12 mV more reducing E(hc), respectively. This condition paradoxically increased the level of mitochondrial oxidation, as demonstrated by redox shifts in mitochondrial roGFP and Trx2. Lastly, either NAC treatment (EC(50) 4 mM) or either GCLC or GCLM overexpression exhibited increased cytotoxicity and the susceptibility to the more reducing milieu was achieved at decreased levels of ROS. Taken together, our findings reveal a novel mechanism by which GSH-dependent reductive stress triggers mitochondrial oxidation and cytotoxicity.

合写作者:Pattraranee Limphong,Joel Pieper,Qiang Liu,Christopher K Rodesch,Elisabeth Christians

第一作者:Huali Zhang(第一作者)

通讯作者:Ivor J Benjamin

学科门类:医学

一级学科:基础医学

期号:2012, 26(4):1442-51.

是否译文:

发表时间:2012-04-02

收录刊物:SCI

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