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The presence of pyruvate carboxylase in the human brain and its role in the survival of cultured human astrocytes

E. Gondáš, A. Kráľová Trančíková, J. Šofranko, P. Majerová, V. Lučanský, M. Dohál, A. Kováč, R. Murín

. 2023 ; 72 (3) : 403-414. [pub] 2023Jul14

Language English Country Czech Republic

Document type Journal Article

Pyruvate carboxylase (PC) is a mitochondrial, biotin-containing enzyme catalyzing the ATP-dependent synthesis of oxaloacetate from pyruvate and bicarbonate, with a critical anaplerotic role in sustaining the brain metabolism. Based on the studies performed on animal models, PC expression was assigned to be glia-specific. To study PC distribution among human neural cells, we probed the cultured human astrocytes and brain sections with antibodies against PC. Additionally, we tested the importance of PC for the viability of cultured human astrocytes by applying the PC inhibitor 3-chloropropane-1,2-diol (CPD). Our results establish the expression of PC in mitochondria of human astrocytes in culture and brain tissue and also into a subpopulation of the neurons in situ. CPD negatively affected the viability of astrocytes in culture, which could be partially reversed by supplementing media with malate, 2-oxoglutarate, citrate, or pyruvate. The provided data estimates PC expression in human astrocytes and neurons in human brain parenchyma. Furthermore, the enzymatic activity of PC is vital for sustaining the viability of cultured astrocytes.

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$a Gondáš, Eduard $u Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University Bratislava, Slovak Republic $u Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University Bratislava, Martin, Slovak Republic $7 xx0306228
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$a Pyruvate carboxylase (PC) is a mitochondrial, biotin-containing enzyme catalyzing the ATP-dependent synthesis of oxaloacetate from pyruvate and bicarbonate, with a critical anaplerotic role in sustaining the brain metabolism. Based on the studies performed on animal models, PC expression was assigned to be glia-specific. To study PC distribution among human neural cells, we probed the cultured human astrocytes and brain sections with antibodies against PC. Additionally, we tested the importance of PC for the viability of cultured human astrocytes by applying the PC inhibitor 3-chloropropane-1,2-diol (CPD). Our results establish the expression of PC in mitochondria of human astrocytes in culture and brain tissue and also into a subpopulation of the neurons in situ. CPD negatively affected the viability of astrocytes in culture, which could be partially reversed by supplementing media with malate, 2-oxoglutarate, citrate, or pyruvate. The provided data estimates PC expression in human astrocytes and neurons in human brain parenchyma. Furthermore, the enzymatic activity of PC is vital for sustaining the viability of cultured astrocytes.
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$a Šofranko, Jakub $7 xx0306229 $u Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University Bratislava, Slovak Republic
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$a Lučanský, Vincent $7 xx0306234 $u Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University Bratislava, Martin, Slovak Republic
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