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Journal of Neuroscience, Vol 13, 2013-2023, Copyright © 1993 by Society for Neuroscience
Glutathione S-transferase isoenzymes in rat brain neurons and glia
JA Johnson, A el Barbary, SE Kornguth, JF Brugge and FL Siegel
Environmental Toxicology Center, University of Wisconsin, Madison 53705.
The glutathione S-transferases (GSTs) constitute a family of cytosolic
isoenzymes and a structurally unrelated microsomal enzyme that is involved
in the detoxication of electrophilic xenobiotics. These enzymes also
participate in the intracellular binding and transport of a broad range of
lipophilic compounds including bilirubin, and hormones such as the
glucocorticoids and thyroid hormones. The present investigation
demonstrates that GSTs are present in neurons of the brainstem, forebrain,
and cerebellum. An isoenzyme-specific distribution of GSTs was found in
cytoplasm, nuclei, and nucleoli. The regional and cellular distribution of
cytosolic GSTs in the brain was studied by immunohistochemistry,
spectrophotometric enzyme assay, and reverse-phase HPLC. Polyclonal
antibody against microsomal GST was strongly reactive with Purkinje cells
throughout the cerebellar cortex, and with neurons in the brainstem and
hippocampus. Nuclei of Purkinje cells and of neurons in the brainstem,
hippocampus, and cerebral cortex were immunopositive for alpha-class GST
1-1 (YaYa), whereas alpha-class GST 2-2 (YcYc) antibody was consistently
immunoreactive with the nucleolus, but not with the nucleus or soma. All
alpha-class GST antibodies studied were reactive, to various degrees, with
astrocytes and choroid plexus; however, ependymal cells of the
subventricular zones were immunonegative. alpha-class GST 8-8 (YkYk)
immunoreactivity was specifically localized to endothelial cells and/or
astrocytic end feet associated with blood vessels. Reverse-phase HPLC
indicated that there were also substantial regional differences in the
pattern of alpha-, mu-, and pi-class GST subunit expression. For example,
the thalamus/hypothalamus had the highest GST activity and greatest
concentration of total GST protein and mu-class GST subunit 6 (Yb3),
whereas the brainstem had the greatest concentration of pi-class GST
subunit (Yp). This regional variation in GST expression may be reflective
of regional differences in cell populations. In cerebellar cortex, the
concentration of mu-class GST subunit 4 (Yb2) was greatest in the flocculus
and lowest in the vermis. This is of clinical interest because the pattern
of expression of mu-class GST subunit 4 (Yb2) in the cerebellum coincides
with the known regional susceptibility of this structure to degeneration
after exposure to toxic or metabolic insults. The vermis is most
susceptible to these insults, whereas the lateral lobes and flocculus are
most resistant.(ABSTRACT TRUNCATED AT 400 WORDS)
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