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dc.contributor.CRUESPUNIVERSIDADE ESTADUAL DE CAMPINASpt_BR
dc.contributor.authorunicampCastilho, Roger Frigério-
dc.typeArtigopt_BR
dc.titleExperimental evidence that maleic acid markedly compromises glutamate oxidation through inhibition of glutamate dehydrogenase and α-ketoglutarate dehydrogenase activities in kidney of developing ratspt_BR
dc.contributor.authorRoginski, Ana Cristina-
dc.contributor.authorCecatto, Cristiane-
dc.contributor.authorWajner, Simone Magagnin-
dc.contributor.authorCamera, Fernanda Dal’Maso-
dc.contributor.authorCastilho, Roger Frigério-
dc.contributor.authorWajner, Moacir-
dc.contributor.authorAmaral, Alexandre Umpierrez-
dc.subjectÁcido propiônicopt_BR
dc.subject.otherlanguagePropionic acidpt_BR
dc.description.abstractMaleic 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 (0.05–5 mM), as well as of propionic (PA) and 3-hydroxypropionic (3OHPA) acids (5 mM) 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 α-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 PAcidemiapt_BR
dc.relation.ispartofMolecular and cellular biochemistry: an international journal for chemical biology in health and diseasept_BR
dc.relation.ispartofabbreviationMol. cell. biochem.pt_BR
dc.publisher.cityNew York, NYpt_BR
dc.publisher.countryEstados Unidospt_BR
dc.publisherSpringerpt_BR
dc.date.issued2019-
dc.date.monthofcirculationAug.pt_BR
dc.language.isoengpt_BR
dc.description.volume458pt_BR
dc.description.firstpage99pt_BR
dc.description.lastpage112pt_BR
dc.rightsFechadopt_BR
dc.sourceScopuspt_BR
dc.identifier.issn0300-8177pt_BR
dc.identifier.eissn1573-4919pt_BR
dc.identifier.doi10.1007/s11010-019-03534-7pt_BR
dc.identifier.urlhttps://link.springer.com/article/10.1007/s11010-019-03534-7pt_BR
dc.description.sponsorshipCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQpt_BR
dc.description.sponsorshipCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESpt_BR
dc.description.sponsorshipFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO GRANDE DO SUL - FAPERGSpt_BR
dc.description.sponsordocumentnumber404883/2013-3pt_BR
dc.description.sponsordocumentnumber01.06.0842-00; 573677/2008-5pt_BR
dc.description.sponsordocumentnumber17/2551-0000/800-6pt_BR
dc.date.available2020-05-14T21:09:00Z-
dc.date.accessioned2020-05-14T21:09:00Z-
dc.description.provenanceSubmitted by Thais de Brito Barroso (tbrito@unicamp.br) on 2020-05-14T21:09:00Z No. of bitstreams: 0. Added 1 bitstream(s) on 2020-08-27T19:17:56Z : No. of bitstreams: 1 2-s2.0-85065012882.pdf: 1637801 bytes, checksum: e3d06ba123ec5683a6b00384bac20f73 (MD5)en
dc.description.provenanceMade available in DSpace on 2020-05-14T21:09:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2019en
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/341471-
dc.contributor.departmentDepartamento de Patologia Clínicapt_BR
dc.contributor.unidadeFaculdade de Ciências Médicaspt_BR
dc.subject.keywordMaleic acidpt_BR
dc.subject.keywordMitochondrial-oxidative metabolismpt_BR
dc.subject.keywordPropionic acidemiapt_BR
dc.subject.keywordRenal failurept_BR
dc.identifier.source2-s2.0-85065012882pt_BR
dc.creator.orcid0000-0003-2338-8717pt_BR
dc.type.formArtigopt_BR
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