Presence and induction of the enzyme NAD(P)H: quinone oxidoreductase 1 in the central nervous system.
NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyzes a reductive detoxification that is thought to protect cells against the adverse effects of quinones and related compounds. NQO1 activity is present in all tissues. Absence of the enzyme produces abnormalities in the redox state and seizures, suggesting an important role of the protein in the central nervous system. Immunohistochemical analysis showed that the protein was found throughout the brain of the adult rat and mouse, with complete absence of the protein in brains from NQO1-/- mice. NQO1 was not seen in any neuronal population, but was localized to Bergmann glial in the cerebellum and a subset of the oligodendrocytes throughout the brain. Prolonged seizures induced in adult rats with kainic acid resulted in an increase in activity of the enzyme throughout the brain, most prominently in the cerebellum, but immunoreactivity did not appear in neurons. Comparison of the axons in the corpus callosum from a wild-type mouse to a knockout mouse showed that myelin is produced in the absence of NQO1, but there appears to be more small-diameter axons in the knockout animal. These results suggest that NQO1 has a role in myelination in the central nervous system or in the insulating/wrapping function of glial cells.
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030-3498, USA. janets@bcm.tmc.edu
Janet L
JL
Stringer
Amos
A
Gaikwad
Bianca N
BN
Gonzales
Delwin J
DJ
Long
Latoia M
LM
Marks
Anil K
AK
Jaiswal
D000818:Animals; D002490:Central Nervous System / Q000737:chemistry* / Q000201:enzymology*; D004790:Enzyme Induction / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000032:analysis* / Q000096:biosynthesis* / Q000235:genetics; D009252:NADPH Dehydrogenase; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D009419:Nerve Tissue Proteins; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D009252:NADPH Dehydrogenase