dc.contributor.author	Ferreira, IL
dc.contributor.author	Cunha-Oliveira, T
dc.contributor.author	Nascimento, MV
dc.contributor.author	Ribeiro, M
dc.contributor.author	Proença, MT
dc.contributor.author	Januário, C
dc.contributor.author	Oliveira, CR
dc.contributor.author	Rego, AC
dc.date.accessioned	2011-11-03T15:56:36Z
dc.date.available	2011-11-03T15:56:36Z
dc.date.issued	2011
dc.description.abstract	In this work we studied the mitochondrial-associated metabolic pathways in Huntington's disease (HD) versus control (CTR) cybrids, a cell model in which the contribution of mitochondrial defects from patients is isolated. HD cybrids exhibited an interesting increase in ATP levels, when compared to CTR cybrids. Concomitantly, we observed increased glycolytic rate in HD cybrids, as revealed by increased lactate/pyruvate ratio, which was reverted after inhibition of glycolysis. A decrease in glucose-6-phosphate dehydrogenase activity in HD cybrids further indicated decreased rate of the pentose-phosphate pathway. ATP levels of HD cybrids were significantly decreased under glycolysis inhibition, which was accompanied by a decrease in phosphocreatine. Nevertheless, pyruvate supplementation could not recover HD cybrids' ATP or phosphocreatine levels, suggesting a dysfunction in mitochondrial use of that substrate. Oligomycin also caused a decrease in ATP levels, suggesting a partial support of ATP generation by the mitochondria. Nevertheless, mitochondrial NADH/NAD(t) levels were decreased in HD cybrids, which was correlated with a decrease in pyruvate dehydrogenase activity and protein expression, suggesting decreased tricarboxylic acid cycle (TCA) input from glycolysis. Interestingly, the activity of alpha-ketoglutarate dehydrogenase, a critical enzyme complex that links the TCA to amino acid synthesis and degradation, was increased in HD cybrids. In accordance, mitochondrial levels of glutamate were increased and alanine was decreased, whereas aspartate and glutamine levels were unchanged in HD cybrids. Conversely, malate dehydrogenase activity from total cell extracts was unchanged in HD cybrids. Our results suggest that inherent dysfunction of mitochondria from HD patients affects cellular bioenergetics in an otherwise functional nuclear background.	por
dc.identifier.citation	Exp Neurol. 2011 Sep;231(1):127-34.	por
dc.identifier.uri	http://hdl.handle.net/10400.4/1108
dc.language.iso	eng	por
dc.peerreviewed	yes	por
dc.publisher	Elsevier	por
dc.subject	Doença de Huntington	por
dc.subject	Células Híbridas	por
dc.title	Bioenergetic dysfunction in Huntington's disease human cybrids	por
dc.type	journal article
dspace.entity.type	Publication
rcaap.rights	openAccess	por
rcaap.type	article	por

Bioenergetic dysfunction in Huntington's disease human cybrids

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