4-Hydroxy-2(E)-nonenal (HNE) catabolism and formation of HNE adducts are modulated by β oxidation of fatty acids in the isolated rat heart

被引:16
作者
Li, Qingling [1 ]
Sadhukhan, Sushabhan [2 ]
Berthiaume, Jessica M. [1 ]
Ibarra, Rafael A. [1 ]
Tang, Hui [3 ]
Deng, Shuang [1 ]
Hamilton, Eric [2 ]
Nagy, Laura E. [1 ,3 ,4 ]
Tochtrop, Gregory P. [2 ]
Zhang, Guo-Fang [1 ]
机构
[1] Case Western Reserve Univ, Dept Nutr, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA
[3] Cleveland Clin, Dept Pathobiol, Cleveland, OH 44195 USA
[4] Cleveland Clin, Dept Gastroenterol, Cleveland, OH 44195 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
4-Hydroxy-2(E)-nonenal; Catabolism; Fatty acid (beta) oxidation; Heart; Lipid peroxidation; Mass isotopomer; MITOCHONDRIAL NADP(+)-ISOCITRATE DEHYDROGENASE; LIPID-PEROXIDATION; METABOLISM; ISCHEMIA; GLUTATHIONE; PROTEINS; PRODUCT; IDENTIFICATION; REPERFUSION; ALDEHYDE;
D O I
10.1016/j.freeradbiomed.2013.01.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We previously reported that a novel metabolic pathway functionally catabolizes 4-hydroxy-2(E)-nonenal (HNE) via two parallel pathways, which rely heavily on beta-oxidation pathways. The hypothesis driving this report is that perturbations of beta oxidation will alter the catabolic disposal of HNE, favoring an increase in the concentrations of HNE and HNE-modified proteins that may further exacerbate pathology. This study employed Langendorff perfused hearts to investigate the impact of cardiac injury modeled by ischemia/reperfusion and, in a separate set of perfusions, the effects of elevated lipid (typically observed in obesity and type II diabetes) by perfusing with increased fatty acid concentrations (1 mM octanoate). During ischemia, HNE concentrations doubled and the glutathione-HNE adduct and 4-hydroxynonanoyl-CoA were increased by 7- and 10-fold, respectively. Under conditions of increased fatty acid, oxidation to 4-hydroxynonenoic acid was sustained; however, further catabolism through beta oxidation was nearly abolished. The inhibition of HNE catabolism was not compensated for by other disposal pathways of HNE, rather an increase in HNE-modified proteins was observed. Taken together, this study presents a mechanistic rationale for the accumulation of HNE and HNE-modified proteins in pathological conditions that involve alterations to beta oxidation, such as myocardial ischemia, obesity, and high-fat diet-induced diseases. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:35 / 44
页数:10
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