Disturbance of bioenergetics and calcium homeostasis provoked by metabolites accumulating in propionic acidemia in heart mitochondria of developing rats

Publication date: Available online 10 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Ana Cristina Roginski, Alessandro Wajner, Cristiane Cecatto, Simone Magagnin Wajner, Roger Frigério Castilho, Moacir Wajner, Alexandre Umpierrez AmaralAbstractPropionic acidemia is caused by lack of propionyl-CoA carboxylase activity. It is biochemically characterized by accumulation of propionic (PA) and 3-hydroxypropionic (3OHPA) acids and clinically by severe encephalopathy and cardiomyopathy. High urinary excretion of maleic acid (MA) and 2-methylcitric acid (2MCA) is also found in the affected patients. Considering that the underlying mechanisms of cardiac disease in propionic acidemia are practically unknown, we investigated the effects of PA, 3OHPA, MA and 2MCA (0.05–5 mM) on important mitochondrial functions in isolated rat heart mitochondria, as well as in crude heart homogenates and cultured cardiomyocytes. MA markedly inhibited state 3 (ADP-stimulated), state 4 (non-phosphorylating) and uncoupled (CCCP-stimulated) respiration in mitochondria supported by pyruvate plus malate or α-ketoglutarate associated with reduced ATP production, whereas PA and 3OHPA provoked less intense inhibitory effects and 2MCA no alterations at all. MA-induced impaired respiration was attenuated by coenzyme A supplementation. In addition, MA significantly inhibited α-ketoglutarate dehydrogenase activity. Similar data were obtained i...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

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Source: Frontiers in Physiology - Category: Physiology Source Type: research
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Source: Circulation Research - Category: Cardiology Authors: Tags: Circ Res Source Type: research
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Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
gannathan Leeb Dog puppy loss by the age of six to eight weeks after normal development is relatively uncommon. Necropsy findings in two spontaneously deceased Belgian Shepherd puppies indicated an abnormal accumulation of material in several organs. A third deceased puppy exhibited mild signs of an inflammation in the central nervous system and an enteritis. The puppies were closely related, raising the suspicion of a genetic cause. Pedigree analysis suggested a monogenic autosomal recessive inheritance. Combined linkage and homozygosity mapping assigned the most likely position of a potential genetic defect to 13 ...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
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Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
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Source: Cellular and Molecular Neurobiology - Category: Cytology Authors: Tags: Cell Mol Neurobiol Source Type: research
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Source: Diabetes and Metabolism Journal - Category: Endocrinology Tags: Diabetes Metab J Source Type: research
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Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
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Source: The American Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Tags: Report Source Type: research
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