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心脏能量代谢的调节:缺血期间氧化还原状态和细胞区室化的作用

Regulation of cardiac energetics: role of redox state and cellular compartmentation during ischemia.

作者信息

Cabrera Marco E, Zhou Lufang, Stanley William C, Saidel Gerald M

机构信息

Department of Pediatrics, Case Western Reserve University, 11100 Euclid Avenue, RBC-389, Cleveland, OH 44106-6011, USA.

出版信息

Ann N Y Acad Sci. 2005 Jun;1047:259-70. doi: 10.1196/annals.1341.023.

DOI:10.1196/annals.1341.023
PMID:16093502
Abstract

The heart is capable of altering its metabolic rate during exercise or ischemia. Under most state transitions, the heart maintains the concentration of adenosine triphosphate (ATP) at relatively constant values, in spite of large fluctuations in metabolic rate or in the delivery of fuels and oxygen. However, the mechanisms responsible for the regulation of cardiac energetics under conditions of increased demand or reduced supply are still under debate. To improve quantitative understanding of the regulation of glycolysis and oxidative phosphorylation under physiological and pathological conditions, it is essential to assess the dynamics of cytosolic and mitochondrial nicotinamide adenine dinucleotide (NAD(+)) and its reduced form (NADH) during stress (e.g., ischemia, exercise). However, at present there are no reliable methods to measure the dynamics of redox state in vivo in these subcellular compartments. In the present study, computer simulations with a mathematical model of myocardial energy metabolism are used to investigate the role of cytosolic and mitochondrial redox states in regulating cardiac energetics during reduced myocardial blood flow.

摘要

心脏能够在运动或缺血期间改变其代谢率。在大多数状态转变过程中,尽管代谢率或燃料及氧气供应存在大幅波动,心脏仍能将三磷酸腺苷(ATP)的浓度维持在相对恒定的值。然而,在需求增加或供应减少的情况下,负责调节心脏能量代谢的机制仍存在争议。为了更好地定量理解生理和病理条件下糖酵解和氧化磷酸化的调节,评估应激(如缺血、运动)期间细胞质和线粒体烟酰胺腺嘌呤二核苷酸(NAD(+))及其还原形式(NADH)的动态变化至关重要。然而,目前尚无可靠的方法来测量这些亚细胞区室中体内氧化还原状态的动态变化。在本研究中,利用心肌能量代谢数学模型进行计算机模拟,以研究细胞质和线粒体氧化还原状态在心肌血流减少期间调节心脏能量代谢中的作用。

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Parallel activation of mitochondrial oxidative metabolism with increased cardiac energy expenditure is not dependent on fatty acid oxidation in pigs.猪心脏能量消耗增加时线粒体氧化代谢的平行激活并不依赖于脂肪酸氧化。
J Physiol. 2007 Mar 15;579(Pt 3):811-21. doi: 10.1113/jphysiol.2006.123828. Epub 2006 Dec 21.
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Modeling cardiac ischemia.
模拟心脏缺血。
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Regulation of lactate production at the onset of ischaemia is independent of mitochondrial NADH/NAD+: insights from in silico studies.缺血开始时乳酸生成的调节独立于线粒体NADH/NAD⁺:来自计算机模拟研究的见解
J Physiol. 2005 Dec 15;569(Pt 3):925-37. doi: 10.1113/jphysiol.2005.093146. Epub 2005 Oct 13.