title: 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.
abstract: We previously reported that a novel metabolic pathway functionally catabolizes 4-hydroxy-2(E)-nonenal (HNE) via two parallel pathways, which rely heavily on β-oxidation pathways. The hypothesis driving this report is that perturbations of β 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 (1mM 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 β 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 β oxidation, such as myocardial ischemia, obesity, and high-fat diet-induced diseases.
authors: Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Qingling
authors: Q
authors: Li
authors: Sushabhan
authors: S
authors: Sadhukhan
authors: Jessica M
authors: JM
authors: Berthiaume
authors: Rafael A
authors: RA
authors: Ibarra
authors: Hui
authors: H
authors: Tang
authors: Shuang
authors: S
authors: Deng
authors: Eric
authors: E
authors: Hamilton
authors: Laura E
authors: LE
authors: Nagy
authors: Gregory P
authors: GP
authors: Tochtrop
authors: Guo-Fang
authors: GF
authors: Zhang
mesh_terms: D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006880:Hydroxy Acids / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D015427:Reperfusion Injury
chemical_list: C406867:4-hydroxynonenoic acid; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D006880:Hydroxy Acids; D005978:Glutathione