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Título: | Mitochondrial complex II participates in normoxic and hypoxic regulation of α-keto acids in the murine heart |
Autor: | Mühling, Jörg; Tiefenbach, Martina; López-Barneo, José CSIC ORCID; Piruat, José I. CSIC; García-Flores, Paula CSIC ORCID; Pfeil, Uwe; Gries, Barbara; Mühlfeld, Christian; Weigand, Markus A.; Kummer, Wolfgang; Weissmann, Norbert; Paddenberg, Renate | Palabras clave: | α-Keto acids α-Ketoisocaproate Complex II Hypoxia Krebs cycle Mitochondrial respiratory chain Right ventricular hypertrophy Succinate dehydrogenase Vascular |
Fecha de publicación: | 1-oct-2010 | Editor: | Elsevier | Citación: | Journal of Molecular and Cellular Cardiology 49(6): 950-961 (2010) | Resumen: | α-Keto acids (α-KAs) are not just metabolic intermediates but are also powerful modulators of different cellular pathways. Here, we tested the hypothesis that α-KA concentrations are regulated by complex II (succinate dehydrogenase = SDH), which represents an intersection between the mitochondrial respiratory chain for which an important function in cardiopulmonary oxygen sensing has been demonstrated, and the Krebs cycle, a central element of α-KA metabolism. SDH subunit D heterozygous (SDHD+/−) and wild-type (WT) mice were housed at normoxia or hypoxia (10% O2) for 4 days or 3 weeks, and right ventricular pressure, right ventricle/(left ventricle + septum) ratio, cardiomyocyte ultrastructure, pulmonary vascular remodelling, ventricular complex II subunit expression, SDH activity and α-KA concentrations were analysed. In both strains, hypoxia induced increases in right ventricular pressure and enhanced muscularization of distal pulmonary arteries. Right ventricular hypertrophy was less severe in SDHD+/− mice although the cardiomyocyte ultrastructure and mitochondrial morphometric parameters were unchanged. Protein amounts of SDHA, SDHB and SDHC, and SDH activity were distinctly reduced in SDHD+/− mice. In normoxic SDHD+/− mice, α-ketoisocaproate concentration was lowered to 50% as compared to WT animals. Right/left ventricular concentration differences and the hypoxia-induced decline in individual α-KAs were less pronounced in SDHD+/− animals indicating that mitochondrial complex II participates in the adjustment of cardiac α-KA concentrations both under normoxic and hypoxic conditions. These characteristics are not related to the hemodynamic consequences of hypoxia-induced pulmonary vascular remodelling, since its extent and right ventricular pressure were not affected in SDHD+/− mice albeit right ventricular hypertrophy was attenuated. | Descripción: | 12 páginas, 11 figuras. | Versión del editor: | http://dx.doi.org/10.1016/j.yjmcc.2010.09.023 | URI: | http://hdl.handle.net/10261/38902 | DOI: | 10.1016/j.yjmcc.2010.09.023 | ISSN: | 0022-2828 |
Aparece en las colecciones: | (IBIS) Artículos |
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