title: Disruption of oxidative phosphorylation and synaptic Na(+), K(+)-ATPase activity by pristanic acid in cerebellum of young rats.
abstract: OBJECTIVE
  Peroxisomal biogenesis disorders (PBD) are inherited disorders clinically manifested by neurological symptoms and brain abnormalities, in which the cerebellum is usually involved. Biochemically, patients affected by these neurodegenerative diseases accumulate branched-chain fatty acids, including pristanic acid (Prist) in the brain and other tissues.
  
  
  METHODS
  In the present investigation we studied the in vitro influence of Prist, at doses found in PBD, on oxidative phosphorylation, by measuring the activities of the respiratory chain complexes I-IV and ATP production, as well as on creatine kinase and synaptic Na(+), K(+)-ATPase activities in rat cerebellum.
  
  
  RESULTS
  Prist significantly decreased complexes I-III (65%), II (40%) and especially II-III (90%) activities, without altering the activities of complex IV of the respiratory chain and creatine kinase. Furthermore, ATP formation and synaptic Na(+), K(+)-ATPase activity were markedly inhibited (80-90%) by Prist. We also observed that this fatty acid altered mitochondrial and synaptic membrane fluidity that may have contributed to its inhibitory effects on the activities of the respiratory chain complexes and Na(+), K(+)-ATPase.
  
  
  CONCLUSIONS
  Considering the importance of oxidative phosphorylation for mitochondrial homeostasis and of Na(+), K(+)-ATPase for the maintenance of cell membrane potential, the present data indicate that Prist compromises brain bioenergetics and neurotransmission in cerebellum. We postulate that these pathomechanisms may contribute to the cerebellar alterations observed in patients affected by PBD in which Prist is accumulated.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Estela Natacha Brandt
authors.initials: EN
authors.lastname: Busanello
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Vannessa Gonçalves Araujo
authors.initials: VG
authors.lastname: Lobato
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Angela
authors.initials: A
authors.lastname: Zanatta
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Carolina Maso
authors.initials: CM
authors.lastname: Viegas
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: César Augusto João
authors.initials: CA
authors.lastname: Ribeiro
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. Electronic address: mwajner@ufrgs.br.
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000503:physiopathology*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000008:administration & dosage*; D006706:Homeostasis; D008564:Membrane Potentials; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D018901:Peroxisomal Disorders / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D009097:Multienzyme Complexes; C002844:pristanic acid; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Energy metabolism; Peroxisomal biogenesis disorders; Pristanic acid; Rat cerebellum; Zellweger syndrome