Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain.
In vertebrates, the interconversion of lactate and pyruvate is catalyzed by the enzyme lactate dehydrogenase. Two distinct subunits combine to form the five tetrameric isoenzymes of lactate dehydrogenase. The LDH-5 subunit (muscle type) has higher maximal velocity (Vmax) and is present in glycolytic tissues, favoring the formation of lactate from pyruvate. The LDH-1 subunit (heart type) is inhibited by pyruvate and therefore preferentially drives the reaction toward the production of pyruvate. There is mounting evidence indicating that during activation the brain resorts to the transient glycolytic processing of glucose. Indeed, transient lactate formation during physiological stimulation has been shown by 1H-magnetic resonance spectroscopy. However, since whole-brain arteriovenous studies under basal conditions indicate a virtually complete oxidation of glucose, the vast proportion of the lactate transiently formed during activation is likely to be oxidized. These in vivo data suggest that lactate may be formed in certain cells and oxidized in others. We therefore set out to determine whether the two isoforms of lactate dehydrogenase are localized to selective cell types in the human brain. We report here the production and characterization of two rat antisera, specific for the LDH-5 and LDH-1 subunits of lactate dehydrogenase, respectively. Immunohistochemical, immunodot, and western-blot analyses show that these antisera specifically recognize their homologous antigens. Immunohistochemistry on 10 control cases demonstrated a differential cellular distribution between both subunits in the hippocampus and occipital cortex: neurons are exclusively stained with the anti-LDH1 subunit while astrocytes are stained by both antibodies. These observations support the notion of a regulated lactate flux between astrocytes and neurons.
Département de Psychiatrie, IUPG Bel-Air, Université de Genéve, Switzerland.
P G
PG
Bittar
Y
Y
Charnay
L
L
Pellerin
C
C
Bouras
P J
PJ
Magistretti
D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D001921:Brain / Q000201:enzymology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis*; D007770:L-Lactate Dehydrogenase / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology*; D051381:Rats
D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase