Increased oxidation of certain glycolysis and energy metabolism enzymes in the frontal cortex in Lewy body diseases.
Lipoxidative damage of aldolase A, enolase 1, and glyceraldehyde dehydrogenase (GAPDH) was found in the frontal cortex in a percentage of aged controls by bidimensional gel electrophoresis, Western blot test, in-gel digestion, and mass spectrometry. Aldolase A and enolase 1 were altered in 12 of 19 cases, whereas oxidation of GAPDH was found in 6 of 19 controls. The three enzymes were oxidized in the frontal cortex in the majority of cases of incidental Parkinson's disease (iPD), PD, and dementia with Lewy bodies (DLB). Differences were statistically significant (chi(2) test) for GAPDH in PD and DLB. Densitometric studies have shown that the ratio of oxidized protein per spot is higher in iPD, PD, and DLB compared with controls. These findings show oxidation of three enzymes linked with glycolysis and energy metabolism in the adult human brain as well as increased oxidation of aldolase A, enolase 1, and GAPDH in the frontal cortex in Lewy body diseases. Modifications of these enzymes may result in decreased activity and may partly account for impaired metabolism and function of the frontal lobe in PD.
Institut Neuropatologia, Servei Anatomia Patològica, Idibell-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain.
Anna
A
Gómez
Isidre
I
Ferrer
D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003720:Densitometry; D015180:Electrophoresis, Gel, Two-Dimensional; D004734:Energy Metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000503:physiopathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D000447:Aldehydes; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D005634:Fructose-Bisphosphate Aldolase; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase; C027576:4-hydroxy-2-nonenal