Changes in the activity of some metabolic enzymes in the heart of SHR rat incurred by transgenic expression of CD36
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ORIGINAL ARTICLE
Changes in the activity of some metabolic enzymes in the heart of SHR rat incurred by transgenic expression of CD36 Dmitry Manakov 1 & David Kolar 1 & Jitka Zurmanova 1 & Michal Pravenec 2 & Jiri Novotny 1 Received: 8 December 2017 / Accepted: 12 June 2018 # University of Navarra 2018
Abstract Hypertension, dyslipidemia, and insulin resistance in the spontaneously hypertensive rat (SHR) can be alleviated by rescuing CD36 fatty acid translocase. The present study investigated whether transgenic rescue of CD36 in SHR could affect mitochondrial function and activity of selected metabolic enzymes in the heart. These analyses were conducted on ventricular preparations derived from SHR and from transgenic strain SHR-Cd36 that expresses a functional wild-type CD36. Our respirometric measurements revealed that mitochondria isolated from the left ventricles exhibited two times higher respiratory activity than those isolated from the right ventricles. Whereas, we did not observe any significant changes in functioning of the mitochondrial respiratory system between both rat strains, enzyme activities of total hexokinase, and both mitochondrial and total malate dehydrogenase were markedly decreased in the left ventricles of transgenic rats, compared to SHR. We also detected downregulated expression of the succinate dehydrogenase subunit SdhB (complex II) and 70 kDa peroxisomal membrane protein in the left ventricles of SHR-Cd36. These data indicate that CD36 may affect in a unique fashion metabolic substrate flexibility of the left and right ventricles. Keywords SHR . CD36 . Heart . Left and right ventricles . Mitochondria . OXPHOS
Introduction High blood pressure is a highly prevalent independent risk factor for cardiovascular disease. Hypertension affects hundreds of millions of people globally [32]. One of its effects is cardiac pressure overload upon which the cardiac muscle reacts with compensatory ventricular hypertrophy. Increased left ventricular mass and hypertrophy are often associated with type II diabetes, obesity and hypercholesteremia, the hallmarks of metabolic syndrome [47]. The spontaneously hypertensive rat (SHR), which was derived from inbred Wistar-Kyoto rats (WKY), is a widely used model of primary hypertension and metabolic syndrome [36]. At some point, a mutation in the gene encoding fatty acid (FA) translocase CD36 occurred that rendered the Cd36 gene * Jiri Novotny [email protected] 1
Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic
2
Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
product nonfunctional in SHR [2]. CD36, newly designated CD36/SR-B2 (cluster of differentiation 36/scavenger receptor B2) [38], together with FA binding proteins, is responsible for the majority of intracellularly transported FA in the heart. Besides powering FA oxidation (FAO), FA regulate energy metabolism through the interaction with peroxisome proliferator-activated receptor [11]. To investigate the impact of CD36 dysfu
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