Role of acetaldehyde and acetate in the development of ethanol-induced cardiac lipidosis, studied in isolated perfused rat hearts.
Role of acetaldehyde and acetate in the development of ethanol-induced cardiac lipidosis, studied in isolated perfused rat hearts.
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在离体灌注大鼠心脏中研究了乙醛和乙酸盐在乙醇诱导的心脏脂质沉积症发展中的作用。
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发表时间：
1983
期刊：
影响因子：
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通讯作者：
I. Hassinen
中科院分区：
文献类型：
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作者：
K. Kiviluoma;I. Hassinen
采用离体灌流大鼠心脏，研究乙醇、乙醛和乙酸对心肌细胞氧化还原状态和脂肪酸代谢的影响。乙醇对细胞氧化还原状态的影响可以忽略不计，但在高浓度下，抑制收缩活动，从而次要的氧消耗。乙醛在浓度低于50 μ M的线粒体游离NAD+/NADH对的氧化还原状态的影响可以忽略不计，研究黄素和烟酰胺核苷酸的表面荧光。在50至500 μ M的浓度下观察到NAD+的减少，而在0.5-1 mM的范围内，该作用是双相的，即，最初的还原之后是氧化，伴随着心率和峰值收缩压的增加。在冠状动脉血流中引起的毫摩尔浓度的醋酸盐。在心肌中发现线粒体乙醛脱氢酶，对乙醛的表观Km为1.1 μ M。乙醛在50 μ M浓度的摄取，氧化，或脂质掺入油酸在心肌没有重大影响。浓度小于2 mM的醋酸盐不影响心肌对油酸盐的摄取，但确实抑制了氧化，并以剂量依赖性方式增强了其与组织脂质的结合。2 mM乙酸导致油酸掺入组织脂质超过30分钟的91%的增加。数据可以解释为显示，乙醛和乙酸，乙醇的代谢产物，对心肌有代谢作用，但只有那些乙酸是显着的浓度在体内乙醇氧化过程中遇到的。醋酸盐可能参与乙醇诱导的心肌脂肪变性的发展，抑制脂肪酸的氧化，并将其引入酯化途径。
Isolated perfused rat hearts were used to study the effects of ethanol, acetaldehyde, and acetate on the cellular redox state and fatty acid metabolism in the myocardium. Ethanol had negligible effects on the cellular redox state but at high concentrations depressed the contractile activity and thereby secondarily the oxygen consumption. Acetaldehyde in concentrations below 50 microM had negligible effects on the redox state of the mitochondrial free NAD+/NADH couple, as studied by surface fluorometry of flavins and nicotinamide nucleotides. A reduction of NAD+ was observed with concentrations between 50 and 500 microM, while in the range of 0.5-1 mM the effect was biphasic, i.e., an initial reduction was followed by oxidation concomitantly with an increase in heart rate and peak systolic pressure. Acetate in millimolar concentrations caused in the coronary flow. A mitochondrial acetaldehyde dehydrogenase was revealed in the myocardium, having an apparent Km of 1.1 microM for acetaldehyde. Acetaldehyde in 50-microM concentration had no major effects on the uptake, oxidation, or lipid incorporation of oleate in the myocardium. Acetate in concentrations less than 2 mM did not affect the uptake of oleate into the myocardium, but did inhibit is oxidation and enhance its incorporation into tissue lipids in a dose-dependent manner. 2 mM acetate caused a 91% increase in oleate incorporation into tissue lipids over 30 min. The data can be interpreted as showing that acetaldehyde and acetate, the metabolites of ethanol, have metabolic effects on the myocardium, but only those of acetate are significant in concentrations encountered during ethanol oxidation in vivo. It is probable that acetate is involved in the development of ethanol-induced myocardial lipidosis, inhibiting the oxidation of fatty acids, and channelling them into the esterification pathway.