Cysteine hydropersulfide reduces lipid peroxidation and protects against myocardial ischaemia-reperfusion injury - Are endogenous persulfides mediators of ischaemic preconditioning?
Cysteine hydropersulfide reduces lipid peroxidation and protects against myocardial ischaemia-reperfusion injury - Are endogenous persulfides mediators of ischaemic preconditioning?
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DOI：
10.1016/j.redox.2023.102605
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发表时间：
2023-04
期刊：
影响因子：
11.4
通讯作者：
Madhani, Melanie
中科院分区：
文献类型：
--
作者：
Griffiths, Kayleigh;Ida, Tomoaki;Morita, Masanobu;Lamb, Reece J.;Lee, Jordan J.;Frenneaux, Michael P.;Fukuto, Jon M.;Akaike, Takaaki;Feelisch, Martin;Madhani, Melanie
关键词：
早期的研究表明，在各种哺乳动物组织中存在过硫化半胱氨酸（CysSSH）和相关的多硫化物物种。CysSSH具有抗氧化和氧化特性，调节氧化还原依赖性信号转导，并已显示出减轻氧化应激。然而，其在心肌缺血-再灌注损伤（IRI）中的功能相关性仍然未知。本研究旨在（1）研究常氧和缺氧条件下心脏中过硫化物的产生和消耗动力学，以及（2）确定在再灌注开始时外源性给予CysSSH供体，半胱氨酸三硫化物（Cys-SSS-Cys）是否通过干扰脂质过氧化来挽救功能障碍和心肌损伤。利用一个完善的离体Langendorff小鼠模型，我们在这里证明，内源性组织浓度的CysSSH上调时，氧气供应受到损害（全球心肌缺血），并迅速恢复到基线水平后，再灌注，提示积极的调节。在一组单独的实验中，发现在再灌注开始时外源性施用Cys-SSS-Cys 10分钟可降低丙二醛（MDA）浓度、4-羟基壬烯醛（4-HNE）蛋白加合物的形成并拯救心脏免受损伤。Cys-SSS-Cys还恢复了缺血后的心脏功能，改善了冠状动脉血流和左心室发展压（LVDP）。总之，这些结果支持的概念，内源性CysSSH起着重要的作用，作为一个“氧化还原预处理”剂，以打击心肌IRI的氧化损伤。
Earlier studies revealed the presence of cysteine persulfide (CysSSH) and related polysulfide species in various mammalian tissues. CysSSH has both antioxidant and oxidant properties, modulates redox-dependent signal transduction and has been shown to mitigate oxidative stress. However, its functional relevance in the setting of myocardial ischaemia-reperfusion injury (IRI) remains unknown. The present study was undertaken to (1) study the dynamics of production and consumption of persulfides under normoxic and hypoxic conditions in the heart, and (2) determine whether exogenous administration of the CysSSH donor, cysteine trisulfide (Cys-SSS-Cys) at the onset of reperfusion rescues functional impairment and myocardial damage by interfering with lipid peroxidation. Utilising a well-established ex vivo Langendorff murine model, we here demonstrate that endogenous tissue concentrations of CysSSH are upregulated when oxygen supply is compromised (global myocardial ischaemia) and rapidly restored to baseline levels upon reperfusion, suggestive of active regulation. In a separate set of experiments, exogenous administration of Cys-SSS-Cys for 10 min at the onset of reperfusion was found to decrease malondialdehyde (MDA) concentrations, formation of 4-hydroxynonenal (4-HNE) protein adducts and rescue the heart from injury. Cys-SSS-Cys also restored post-ischaemic cardiac function, improving both coronary flow and left ventricular developed pressure (LVDP). Taken together, these results support the notion that endogenous CysSSH plays an important role as a “redox preconditioning” agent to combat the oxidative insult in myocardial IRI.
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硫化物分解代谢可以改善低氧脑损伤。
影响因子：
16.6
作者：
Marutani E;Morita M;Hirai S;Kai S;Grange RMH;Miyazaki Y;Nagashima F;Traeger L;Magliocca A;Ida T;Matsunaga T;Flicker DR;Corman B;Mori N;Yamazaki Y;Batten A;Li R;Tanaka T;Ikeda T;Nakagawa A;Atochin DN;Ihara H;Olenchock BA;Shen X;Nishida M;Hanaoka K;Kevil CG;Xian M;Bloch DB;Akaike T;Hindle AG;Motohashi H;Ichinose F
通讯作者：
Ichinose F
影响因子：
5.1
作者：
ABDOLRASULNIA, R;WOOD, JL
通讯作者：
WOOD, JL
DOI：
10.1152/ajpheart.00129.2010
发表时间：
2010-09
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Madhani M;Hall AR;Cuello F;Charles RL;Burgoyne JR;Fuller W;Hobbs AJ;Shattock MJ;Eaton P
通讯作者：
Eaton P
影响因子：
--
作者：
Rodrigo R;Libuy M;Feliú F;Hasson D
通讯作者：
Hasson D
影响因子：
3.5
作者：
Fukuto JM;Ignarro LJ;Nagy P;Wink DA;Kevil CG;Feelisch M;Cortese-Krott MM;Bianco CL;Kumagai Y;Hobbs AJ;Lin J;Ida T;Akaike T
通讯作者：
Akaike T