Increased expression of glyceraldehyde-3-phosphate dehydrogenase in cultured astrocytes following exposure to manganese.
Manganism is a disorder characterized by hyperintensities in basal ganglia structures on magnetic resonance imaging which may be the consequence of manganese deposition in these areas. Since manganese is taken up avidly into astrocytes and is known to interfere with cerebral energy metabolism, we studied the effect of this metal on the expression and activity of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in primary cultures of astrocytes. Treatment with 100 microM manganese for 7 days increased both the Vmax and Km values for GAPDH which was not reproducible with other divalent metals. Using RT-PCR, increased GAPDH expression was detected in cells exposed to manganese compared with controls. No changes in cytochrome oxidase activity or ATP levels were observed, and lactate production was unaffected, in manganese-treated cells. These findings provide evidence of a possible role for GAPDH in the mediation of the effects of manganese on central nervous system function.
Hazell
A S
AS
Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), Quebec, Canada.
Desjardins
P
P
Butterworth
R F
RF
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology*; D002470:Cell Survival; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D017895:Manganese Compounds / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002712:Chlorides; D017895:Manganese Compounds; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D003576:Electron Transport Complex IV; C025340:manganese chloride