The methyl donor S-adenosylmethionine prevents liver hypoxia and dysregulation of mitochondrial bioenergetic function in a rat model of alcohol-induced fatty liver disease.
The methyl donor S-adenosylmethionine prevents liver hypoxia and dysregulation of mitochondrial bioenergetic function in a rat model of alcohol-induced fatty liver disease.
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DOI：
10.1016/j.redox.2016.08.005
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发表时间：
2016-10
期刊：
影响因子：
11.4
通讯作者：
Bailey, Shannon M.
中科院分区：
文献类型：
--
作者：
King, Adrienne L.;Mantena, Sudheer K.;Andringa, Kelly K.;Millender-Swain, Telisha;Dunham-Snary, Kimberly J.;Oliva, Claudia R.;Griguer, Corinne E.;Bailey, Shannon M.
线粒体功能障碍和生物能量应激在酒精性肝病的病因学中起重要作用。我们实验室之前的研究表明，初级甲基供体s -腺苷甲硫氨酸（SAM）可以最大限度地减少酒精引起的肝脏几种线粒体功能的破坏。在此，我们扩展了这些早期的观察结果，以确定SAM对酒精毒性的有益作用是否延伸到线粒体呼吸对一氧化氮（NO）抑制的反应性的变化、线粒体通透性转化（MPT）孔的诱导以及肝脏缺氧状态的变化。为此，雄性Sprague-Dawley大鼠配对喂食含SAM和不含SAM的对照和含酒精的液体饲料5周，并检测肝脏缺氧、线粒体呼吸、MPT孔诱导和no依赖的呼吸控制。慢性酒精喂养显著增强肝脏缺氧，而补充SAM则减轻了酒精喂养大鼠肝脏缺氧。添加SAM可防止酒精介导的线粒体状态3呼吸和细胞色素c氧化酶活性的降低。从酒精喂养的大鼠肝脏中分离的线粒体对钙介导的MPT孔诱导（即线粒体肿胀）比配对喂养的对照组的线粒体更敏感，而SAM处理使酒精喂养的大鼠对钙诱导的线粒体肿胀的敏感性正常化。与成对喂养的对照组相比，酒精喂养的大鼠肝脏线粒体对no依赖性呼吸抑制的敏感性增加。相比之下，从SAM处理的酒精喂养大鼠肝脏中分离的线粒体对no介导的呼吸抑制的敏感性没有变化。总的来说，这些发现表明，SAM对酒精毒性的肝保护作用部分是通过线粒体机制介导的，该机制涉及保存关键的线粒体生物能量参数和减少缺氧应激。大鼠分别饲喂对照组和酒精饲粮±s -腺苷蛋氨酸（SAM） 5周。SAM可预防酒精性肝缺氧。SAM使酒精喂养的大鼠线粒体呼吸正常化。SAM对酒精喂养大鼠线粒体通透性转变的标准化敏感性。SAM使酒精喂养大鼠一氧化氮介导的呼吸抑制正常化。
Mitochondrial dysfunction and bioenergetic stress play an important role in the etiology of alcoholic liver disease. Previous studies from our laboratory show that the primary methyl donor S-Adenosylmethionine (SAM) minimizes alcohol-induced disruptions in several mitochondrial functions in the liver. Herein, we expand on these earlier observations to determine whether the beneficial actions of SAM against alcohol toxicity extend to changes in the responsiveness of mitochondrial respiration to inhibition by nitric oxide (NO), induction of the mitochondrial permeability transition (MPT) pore, and the hypoxic state of the liver. For this, male Sprague-Dawley rats were pair-fed control and alcohol-containing liquid diets with and without SAM for 5 weeks and liver hypoxia, mitochondrial respiration, MPT pore induction, and NO-dependent control of respiration were examined. Chronic alcohol feeding significantly enhanced liver hypoxia, whereas SAM supplementation attenuated hypoxia in livers of alcohol-fed rats. SAM supplementation prevented alcohol-mediated decreases in mitochondrial state 3 respiration and cytochrome c oxidase activity. Mitochondria isolated from livers of alcohol-fed rats were more sensitive to calcium-mediated MPT pore induction (i.e., mitochondrial swelling) than mitochondria from pair-fed controls, whereas SAM treatment normalized sensitivity for calcium-induced swelling in mitochondria from alcohol-fed rats. Liver mitochondria from alcohol-fed rats showed increased sensitivity to NO-dependent inhibition of respiration compared with pair-fed controls. In contrast, mitochondria isolated from the livers of SAM treated alcohol-fed rats showed no change in the sensitivity to NO-mediated inhibition of respiration. Collectively, these findings indicate that the hepato-protective effects of SAM against alcohol toxicity are mediated, in part, through a mitochondrial mechanism involving preservation of key mitochondrial bioenergetic parameters and the attenuation of hypoxic stress. Rats were fed control and alcohol diets±S-Adenosylmethionine (SAM) for 5 weeks. SAM prevented alcohol-induced liver hypoxia. SAM normalized mitochondrial respiration in alcohol-fed rats. SAM normalized sensitivity to undergo the mitochondrial permeability transition in alcohol-fed rats. SAM normalized nitric oxide-mediated respiratory inhibition in alcohol-fed rats.
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DOI：
10.1152/ajpgi.00332.2009
发表时间：
2010-05-01
影响因子：
4.5
作者：
Andringa, Kelly K.;King, Adrienne L.;Bailey, Shannon M.
通讯作者：
Bailey, Shannon M.
DOI：
10.1152/ajpgi.00044.2006
发表时间：
2006-11-01
影响因子：
4.5
作者：
Bailey, Shannon M.;Robinson, Gloria;Darley-Usmar, Victor
通讯作者：
Darley-Usmar, Victor
DOI：
10.1152/ajpgi.1996.271.3.g494
发表时间：
1996-09-01
影响因子：
4.5
作者：
Arteel, GE;Raleigh, JA;Thurman, RG
通讯作者：
Thurman, RG
影响因子：
13.8
作者：
Cooper, CE;Patel, RP;Darley-Usmar, VM
通讯作者：
Darley-Usmar, VM
影响因子：
13.5
作者：
GARCIARUIZ, C;MORALES, A;FERNANDEZCHECA, JC
通讯作者：
FERNANDEZCHECA, JC