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Type: Artigo
Title: Experimental evidence that maleic acid markedly compromises glutamate oxidation through inhibition of glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase activities in kidney of developing rats
Author: Roginski, Ana Cristina
Cecatto, Cristiane
Wajner, Simone Magagnin
Camera, Fernanda Dal'Maso
Castilho, Roger Frigerio
Wajner, Moacir
Amaral, Alexandre Umpierrez
Abstract: Maleic acid (MA), which has been reported to be highly excreted in propionic acidemia (PAcidemia), was demonstrated to cause nephropathy by bioenergetics impairment and oxidative stress, but the effects on kidney mitochondrial respiration has not yet been properly investigated. Therefore, the present study investigated the effects of MA (0.05-5mM), as well as of propionic (PA) and 3-hydroxypropionic (3OHPA) acids (5mM) that accumulate in PAcidemia, on mitochondrial respiration supported by glutamate, glutamate plus malate or succinate in mitochondrial fractions and homogenates from rat kidney, as well as in permeabilized kidney cells. MA markedly decreased oxygen consumption in state 3 (ADP-stimulated) and uncoupled (CCCP-stimulated) respiration in glutamate and glutamate plus malate-respiring mitochondria, with less prominent effects when using succinate. We also found that PA significantly decreased state 3 and uncoupled respiration in glutamate- and glutamate plus malate-supported mitochondria, whereas 3OHPA provoked milder or no changes. Furthermore, glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase activities necessary for glutamate oxidation were significantly inhibited by MA in a dose-dependent and competitive fashion. The MA-induced decrease of state 3 and uncoupled respiration found in mitochondrial fractions were also observed in homogenates and permeabilized renal cells that better mimic the in vivo cellular milieu. Taken together, our data indicate that MA, and PA to a lesser extent, disturb mitochondrial-oxidative metabolism in the kidney with the involvement of critical enzymes for glutamate oxidation. It is postulated that our present findings may be possibly involved in the chronic renal failure observed in patients with PAcidemia
Subject: Ácido propiônico
Country: Estados Unidos
Editor: Springer
Rights: Fechado
Identifier DOI: 10.1007/s11010-019-03534-7
Date Issue: 2019
Appears in Collections:FCM - Artigos e Outros Documentos

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