caa a22 4500 463254570 CHVBK 20180405153351.0 cr unu---uuuuu 170326e20070601xx s 000 0 eng 10.1007/s10571-007-9143-3 doi (NATIONALLICENCE)springer-10.1007/s10571-007-9143-3 Isovaleric Acid Reduces Na+, K+-ATPase Activity in Synaptic Membranes from Cerebral Cortex of Young Rats [Elektronische Daten] [César Ribeiro, Fabrício Balestro, Vanessa Grando, Moacir Wajner] 1. Patients affected by isovaleric acidemia (IVAcidemia) suffer from acute episodes of encephalopathy. However, the mechanisms underlying the neuropathology of this disease are poorly known. The objective of the present study was to investigate the in vitro effects of the metabolites that predominantly accumulate in IVAcidemia, namely isovaleric acid (IVA), 3-hydroxyisovaleric acid (3-OHIVA) and isovalerylglycine (IVG), on important parameters of energy metabolism, such as 14CO2 production from acetate and the activities of the respiratory chain complexes I-IV, creatine kinase and Na+, K+-ATPase in synaptic plasma membranes from cerebral cortex homogenates of 30-day-old rats. 2. We observed that 3-OHIVA acid and IVG did not affect all the parameters analyzed. Similarly, 14CO2 production from acetate (Krebs cycle activity), the activities of creatine kinase, and of the respiratory chain complexes was not modified by IVA. In contrast, IVA exposition to cortical homogenates provoked a marked inhibition of Na+, K+-ATPase activity. However, this activity was not changed when IVA was directly exposed to purified synaptic plasma membranes, suggesting an indirect effect of this organic acid on the enzyme. Furthermore, pretreatment of cortical homogenates with α-tocopherol and creatine totally prevented IVA-induced inhibition on Na+, K+-ATPase activity from synaptic plasma membranes, whereas glutathione (GSH) and the NO synthase inhibitor Nω-nitro-l-arginine methyl ester (L-NAME) did not alter this inhibition. 3. These data indicate that peroxide radicals were probably involved in this inhibitory effect. Since Na+, K+-ATPase is a critical enzyme for normal brain development and functioning and necessary to maintain neuronal excitability, it is presumed that the inhibitory effect of IVA on this activity may be involved in the pathophysiology of the neurological dysfunction of isovaleric acidemic patients. Springer Science+Business Media, LLC, 2007 Na+ nationallicence K+-ATPase nationallicence energy metabolism nationallicence isovaleric acid nationallicence isovaleric acidemia nationallicence respiratory chain nationallicence citric acid cycle nationallicence cerebral cortex nationallicence Ribeiro César Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil aut Balestro Fabrício Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil aut Grando Vanessa Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil aut Wajner Moacir Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil aut Cellular and Molecular Neurobiology Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 27/4(2007-06-01), 529-540 0272-4340 27:4<529 2007 27 10571 https://doi.org/10.1007/s10571-007-9143-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-007-9143-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ribeiro César Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Balestro Fabrício Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Grando Vanessa Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Wajner Moacir Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 27/4(2007-06-01), 529-540 0272-4340 27:4<529 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer