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Methylmalonic Acid Compromises Respiration and Reduces the Expression of Differentiation Markers of SH-SY5Y Human Neuroblastoma Cells.
da Costa, Renata T; Dos Santos, Marcella B; Silva, Izabel C S; de Almeida, Raquel P; Teruel, Marcela S; Carrettiero, Daniel C; Ribeiro, César A J.
Afiliação
  • da Costa RT; Universidade Federal do ABC (UFABC), Centro de Ciências Naturais e Humanas (CCNH), São Bernardo do Campo, SP 09606-070, Brazil.
  • Dos Santos MB; Universidade Federal do ABC (UFABC), Centro de Ciências Naturais e Humanas (CCNH), São Bernardo do Campo, SP 09606-070, Brazil.
  • Silva ICS; Universidade Federal do ABC (UFABC), Centro de Ciências Naturais e Humanas (CCNH), São Bernardo do Campo, SP 09606-070, Brazil.
  • de Almeida RP; Universidade Federal do ABC (UFABC), Centro de Ciências Naturais e Humanas (CCNH), São Bernardo do Campo, SP 09606-070, Brazil.
  • Teruel MS; Universidade Federal do ABC (UFABC), Centro de Ciências Naturais e Humanas (CCNH), São Bernardo do Campo, SP 09606-070, Brazil.
  • Carrettiero DC; Universidade Federal do ABC (UFABC), Centro de Ciências Naturais e Humanas (CCNH), São Bernardo do Campo, SP 09606-070, Brazil.
  • Ribeiro CAJ; Universidade Federal do ABC (UFABC), Centro de Ciências Naturais e Humanas (CCNH), São Bernardo do Campo, SP 09606-070, Brazil.
ACS Chem Neurosci ; 12(14): 2608-2618, 2021 07 21.
Article em En | MEDLINE | ID: mdl-34191487
Methylmalonic acidemia is a rare metabolic disorder caused by the deficient activity of l-methylmalonyl-CoA mutase or its cofactor 5-deoxyadenosylcobalamin and is characterized by accumulation of methylmalonic acid (MMA) and alternative metabolites. The brain is one of the most affected tissues and neurologic symptoms, characterized by seizures, mental retardation, psychomotor abnormalities, and coma, commonly appear in newborns. The molecular mechanisms of neuropathogenesis in methylmalonic acidemia are still poorly understood, specifically regarding the impairments in neuronal development, maturation, and differentiation. In this study, we investigated the effects of MMA in both undifferentiated and differentiated phenotypes of SH-SY5Y human neuroblastoma cells. We observed an increase in glucose consumption and reduction in respiratory parameters of both undifferentiated and differentiated cells after exposition to MMA, suggesting that differentiated cells are slightly more prone to perturbations in respiratory parameters by MMA than undifferentiated cells. Next, we performed qPCR of mature neuronal-specific gene markers and measured mitochondrial functioning to evaluate the role of MMA during differentiation. Our results showed that MMA impairs the respiratory parameters only at the late stage of differentiation and downregulates the transcriptional gene profile of mature neuronal markers neuron-specific enolase (ENO2) and synaptophysin (SYP). Altogether, our findings point out important changes observed during neuronal maturation and energetic stress vulnerability that can play a role in the neurological clinical symptoms at the newborn period and reveal important molecular mechanisms that could help the screening of targets to new approaches in the therapies of this disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Metilmalônico / Neuroblastoma Limite: Humans / Newborn Idioma: En Revista: ACS Chem Neurosci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Metilmalônico / Neuroblastoma Limite: Humans / Newborn Idioma: En Revista: ACS Chem Neurosci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos