From the Cover: Alcohol Inhibition of the Enzymatic Activity of Glyceraldehyde 3-Phosphate Dehydrogenase Impairs Cardiac Glucose Utilization, Contributing to Alcoholic Cardiomyopathy
From the Cover: Alcohol Inhibition of the Enzymatic Activity of Glyceraldehyde 3-Phosphate Dehydrogenase Impairs Cardiac Glucose Utilization, Contributing to Alcoholic Cardiomyopathy
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封面：酒精抑制 3-磷酸甘油醛脱氢酶的酶活性会损害心脏葡萄糖的利用，导致酒精性心肌病
DOI：
10.1093/toxsci/kfx140
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发表时间：
2017-10
影响因子：
3.8
通讯作者：
Tan Yi
中科院分区：
文献类型：
--
作者：
Yan Xiaoqing;Wu Lianpin;Lin Qian;Dai Xiaozhen;Hu Haiqi;Wang Kai;Zhang Chi;Shao Minglong;Cai Lu;Tan Yi
大量饮酒可诱发心肌病，并与心脏代谢变化有关。代谢改变在酒精性心肌病发展中的作用仍然很大程度上未知，但在本研究中进行了研究。研究人员用酒精或等热量控制饮食喂养小鼠2个月，观察慢性酒精摄入对心脏损伤的影响。在动物心脏和H9c2细胞培养中检测了酒精诱导的代谢改变和病理改变的信号通路。与对照组相比，酒精喂养小鼠的心脏表现出心脏氧化应激、细胞死亡、纤维化反应、肥厚重塑，并最终发展为心功能障碍。通过超氧化物歧化酶模拟物MnTMPyP（111）治疗，所有这些有害影响都可以得到改善。一项机制研究表明，慢性酒精暴露增强了调节脂肪酸摄取的蛋白质的表达，但损害了参与线粒体脂肪酸氧化的蛋白质的表达，线粒体脂肪酸氧化使心脏补偿地适应了次优能量来源——葡萄糖。然而，慢性酒精暴露也会损害由甘油醛-3-磷酸脱氢酶调节的糖酵解能量产生步骤，该步骤进一步反馈增强葡萄糖摄取信号和糖酵解中间产物果糖的积累，从而加重酒精诱导的心脏氧化应激、细胞死亡和重构。所有这些代谢异常改变均可通过MnTMPyP治疗正常化，同时心肌细胞死亡和重构也有显著改善。这些结果表明，酒精诱导的氧化应激和葡萄糖代谢改变是酒精性心肌病发生的原因。
Heavy consumption of alcohol induces cardiomyopathy and is associated with metabolic changes in the heart. The role of altered metabolism in the development of alcoholic cardiomyopathy remains largely unknown but is examined in the present study. The effect of chronic alcohol consumption on cardiac damage was examined in mice fed an alcohol or isocaloric control diet for 2 months. Signaling pathways of alcohol-induced metabolic alteration and pathologic changes were examined in both animal hearts and H9c2 cell cultures. Compared with controls, the hearts from the alcohol-fed mice exhibited cardiac oxidative stress, cell death, a fibrotic response, hypertrophic remodeling, and the eventual development of cardiac dysfunction. All these detrimental effects could be ameliorated by superoxide dismutase mimic Mn (111) tetrakis 1-methyl 4-pyridylporphyrin pentachloride (MnTMPyP) therapy. A mechanistic study showed that chronic alcohol exposure enhanced the expression of proteins regulating fatty acid uptake but impaired the expression of proteins involved in mitochondrial fatty acid oxidation, which compensatively geared the heart to the suboptimal energy source, glucose. However, chronic alcohol exposure also impaired the glycolytic energy production step regulated by glyceraldehyde-3-phosphate dehydrogenase, which further feeds back to enhance glucose uptake signaling and the accumulation of glycolytic intermediate product fructose, resulting in aggravation of alcohol-induced cardiac oxidative stress, cell death, and remodeling. All these dysmetabolic alterations could be normalized by MnTMPyP treatment, along with significant improvement in cardiac cell death and remodeling. These results demonstrate that alcohol-induced oxidative stress and altered glucose metabolism are causal factors for the development of alcoholic cardiomyopathy.
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DOI：
10.1111/acer.12459
发表时间：
2014-07
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Umoh NA;Walker RK;Al-Rubaiee M;Jeffress MA;Haddad GE
通讯作者：
Haddad GE
DOI：
10.1016/j.bbadis.2014.06.030
发表时间：
2015-02
影响因子：
6.2
作者：
Varga, Zoltan V.;Giricz, Zoltan;Liaudet, Lucas;Hasko, Gyoergy;Ferdinandy, Peter;Pacher, Pal
通讯作者：
Pacher, Pal
影响因子：
4
作者：
F. Beier;Silvia Vornehm;E. Pöschl;K. von der Mark;M. Lammi
通讯作者：
F. Beier;Silvia Vornehm;E. Pöschl;K. von der Mark;M. Lammi
影响因子：
5
作者：
Xiaochun Zhang;Aaron L Klein;Nicholas S Alberle;F. Norby;B. H. Ren;J. Duan;Jun Ren
通讯作者：
Xiaochun Zhang;Aaron L Klein;Nicholas S Alberle;F. Norby;B. H. Ren;J. Duan;Jun Ren
影响因子：
4.3
作者：
Jing, Ling;Jin, Cheng-mei;Zhou, Li-jun
通讯作者：
Zhou, Li-jun