Effects of homocysteine on metabolic pathways in cultured astrocytes

Neurochemistry International
Ying Jin, L Brennan

Abstract

Homocysteine is an amino acid that is an important risk factor for several neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Increased homocysteine levels induce neuronal cell death in a variety of neuronal types. However, very few studies have probed the effects of homocysteine in astrocytes. The present study investigated the effects of homocysteine on primary cultures of astrocytes by exposing astrocytes to 400 microM homocysteine for 20 h. Metabolic extracts of cells were prepared following a 4-h incubation in minimum medium with 5.5 mM [U-(13)C]glucose in the presence or absence of homocysteine and analysed using (13)C NMR. The expression level of pyruvate dehydrogenase kinase isoform 2 (PDK-2), NAD(P)H levels and mitochondrial membrane potential responses were investigated following culture with homocysteine. Metabolomic analysis was performed using (1)H NMR spectroscopy and pattern recognition analysis. Following incubation with homocysteine there was a significant decrease (48%) in the ratio of flux through pyruvate carboxylase (PC) and pyruvate dehydrogenase (PDH) which was due to an increased flux through PDH. In addition, homocysteine culture resulted in a significant reduction in PDK-2 protein ...Continue Reading

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Citations

May 28, 2010·Neuropsychiatric Disease and Treatment·Steven F Werder
Nov 19, 2010·Bioanalysis·Iola F DuarteAna M Gil
Jun 21, 2011·Trends in Pharmacological Sciences·Jia-Min ZhuoDomenico Praticò
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Nov 17, 2012·Biochimica Et Biophysica Acta·Martina WallaceLorraine Brennan
Mar 4, 2017·Molecular Neurobiology·Aline LongoniAngela T S Wyse
Dec 15, 2019·International Journal of Molecular Sciences·Maria KovalskaJan Lehotsky
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