Cardiomyocyte-derived mitochondrial superoxide causes myocardial electrical remodeling by downregulating potassium channels and related molecules.
Cardiomyocyte-derived mitochondrial superoxide causes myocardial electrical remodeling by downregulating potassium channels and related molecules.
复制标题
心肌细胞来源的线粒体超氧化物通过下调钾通道和相关分子引起心肌电重塑。
DOI：
10.1253/circj.cj-13-1587
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
J. Ako
中科院分区：
文献类型：
--
作者：
Sayaka Kurokawa;S. Niwano;H. Niwano;M. Murakami;Shoko Ishikawa;Yoshihiko Masaki;H. Tamaki;Toshihiko Toda;Y. Noda;Takahiko Shimizu;T. Izumi;J. Ako
背景
本研究利用L-丁硫氨酸-亚磺胺处理杂合子心肌/肌肉特异性锰超氧化物歧化酶缺陷(H/M-Sod2(+/-))小鼠，探讨高氧化应激在心肌电重构中的作用。
方法和结果
将H/M-Sod2(+/-)和野生型(WT)小鼠随机分为4组：H/M-Sod2(+/-)+BSO组、H/M-Sod2(+/-)对照组、H/M-Sod2(+/-)对照组和WT对照组。测定心室有效不应期(ERP)和单相动作电位时程(MAPd)。同时检测氧化应激、钾通道相关分子和钾通道相互作用蛋白-2(KChIP2)水平。H/M-Sod2(+/-)+BSO组MAPD20、MAPD90和ERP较其他组显著延长(MAPD20：14±1比11±1 ms，MAPD90：77±7比58±4 ms，ERP：61±6比41±3 ms，H/M-Sod2(+/-)+BSO比WT对照组；P<；0.05)。H/M-Sod2(+/-)+BSO组与WT+BSO组比较，心肌线粒体超氧化物歧化和过氧化氢生成增加(P<；0.05)。实时定量RT-PCR和Western blotting显示，Kv4.2在两个BSO处理组中表达下调，而KChIP2表达仅在H/M-Sod2(+/-)+BSO组下调(P<；0.05)。
结论
BSO处理引起H/M-Sod2(+/-)小鼠心肌高氧化应激。钾通道表达和功能的改变被认为参与了该模型的电重构机制。
BACKGROUND
This study was designed to investigate the role of a primary hyperoxidative stress in myocardial electrical remodeling using heterozygous heart/muscle-specific manganese superoxide dismutase-deficient (H/M-Sod2(+/-)) mice treated with L-buthionine-sulfoximine (BSO).
METHODS AND RESULTS
Both H/M-Sod2(+/-)and wild-type (WT) mice were treated with intra-peritoneal BSO or saline for 7 days, and divided into 4 groups: H/M-Sod2(+/-)+BSO, WT+BSO, H/M-Sod2(+/-)control, and WT control. The ventricular effective refractory period (ERP) and the monophasic action potential duration (MAPD) were determined. Levels of oxidative stress, potassium channel-related molecules, and K(+)channel-interacting protein-2 (KChIP2) were also evaluated. The H/M-Sod2(+/-)+BSO group exhibited markedly prolonged MAPD20, MAPD90 and ERP in comparison with the other groups (MAPD20: 14 ± 1 vs. 11 ± 1 ms, MAPD90: 77 ± 7 vs. 58 ± 4 ms, ERP: 61 ± 6 vs. 41 ± 3 ms, H/M-Sod2(+/-)+BSO vs. WT control; P<0.05). Mitochondrial superoxide and hydrogen peroxide formation in the myocardium increased in the H/M-Sod2(+/-)+BSO group in comparison with the WT+BSO group (P<0.05). Real-time RT-PCR and Western blotting revealed that Kv4.2 expression was downregulated in both BSO-treated groups, whereas KChIP2 expression was downregulated only in the H/M-Sod2(+/-)+BSO group (P<0.05).
CONCLUSIONS
BSO treatment caused hyperoxidative stress in the myocardium of H/M-Sod2(+/-)mice. Changes in the expression and function of potassium channels were considered to be involved in the mechanism of electrical remodeling in this model.
氧化应激破坏心脏连接子的连接。
DOI：
10.1172/jci41780
发表时间：
2010
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Tomaselli,GordonF
通讯作者：
Tomaselli,GordonF
DOI：
10.1073/pnas.86.2.471
发表时间：
1989-01-01
影响因子：
11.1
作者：
MARTENSSON, J;MEISTER, A
通讯作者：
MEISTER, A
梗死后大鼠心脏中谷胱甘肽和 K(+) 通道的重塑。
DOI：
10.1152/ajpheart.00894.2001
发表时间：
2002
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Rozanski,GeorgeJ;Xu,Zhi
通讯作者：
Xu,Zhi