Evaluation of a dithiocarbamate derivative as a model of thiol oxidative stress in H9c2 rat cardiomyocytes.
Evaluation of a dithiocarbamate derivative as a model of thiol oxidative stress in H9c2 rat cardiomyocytes.
复制标题
在H9C2大鼠心肌细胞中，评估二硫代氨基酯衍生物作为硫醇氧化应激的模型。
DOI：
10.1016/j.freeradbiomed.2014.02.022
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发表时间：
2014-05
影响因子：
7.4
通讯作者：
Seefeldt, Teresa
中科院分区：
文献类型：
--
作者：
Xie, Jiashu;Potter, Ashley;Xie, Wei;Lynch, Christophina;Seefeldt, Teresa
关键词：
Thiol redox state (TRS) refers to the balance between reduced thiols and their corresponding disulfides and is mainly reflected by the ratio of reduced and oxidized glutathione (GSH/GSSG). A decrease in GSH/GSSG, which reflects a state of thiol oxidative stress, as well as thiol modifications such as S-glutathionylation have been shown to have important implications in a variety of cardiovascular diseases. Therefore, research models for inducing thiol oxidative stress are important tools for studying the pathophysiology of these disease states as well as examining the impact of pharmacological interventions on thiol pathways. The purpose of this study is to evaluate the use of a dithiocarbamate derivative, 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl] propionic acid (2-AAPA) as a pharmacological model of thiol oxidative stress by examining the extent of thiol modifications induced in H9c2 rat cardiomyocytes and its impact on cellular functions. The extent of thiol oxidative stress produced by 2-AAPA was also compared to other models of oxidative stress including hydrogen peroxide (H2O2), diamide, buthionine sulfoximine (BSO) and N,N′-bis(2-chloroethyl)-N-nitroso-urea (BCNU). Results indicated that 2-AAPA effectively inhibited glutathione reductase (GR) and thioredoxin reductase (TrxR) activities and decreased the GSH/GSSG ratio by causing a significant accumulation of GSSG. 2-AAPA also increased the formation of protein disulfides as well as S-glutathionylation. The alteration in TRS lead to loss of mitochondrial membrane potential, release of cytochrome c and an increase in reactive oxygen species (ROS) production. Compared to other models, 2-AAPA is more potent in creating a state of thiol oxidative stress with lower cytotoxicity, higher specificity and more pharmacological relevance, and could be utilized as a research tool to study TRS-related normal and abnormal biochemical processes in cardiovascular diseases.
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DOI：
10.1016/j.jpba.2008.08.033
发表时间：
2008-12-15
影响因子：
3.4
作者：
Chen, Wei;Zhao, Yong;Seefeldt, Teresa;Guan, Xiangming
通讯作者：
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影响因子：
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2008-07-01
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DOI：
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发表时间：
2003-09-01
影响因子：
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作者：
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影响因子：
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作者：
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Forman, HJ