Lh. Overby et al., UNIQUE DISTRIBUTION PROFILES OF GLUTATHIONE S-TRANSFERASES IN REGIONSOF KIDNEY, URETER, AND BLADDER OF RABBIT, Laboratory investigation, 70(4), 1994, pp. 468-478
BACKGROUND: Glutathione S-transferases detoxify a broad range of exoge
nous compounds, but are important also in the metabolism of endogenous
compounds. Physiologically relevant substrates are the endoperoxide a
nd hydroperoxide metabolites of arachidonic acid that play important r
oles in many tissues including the kidney. EXPERIMENTAL DESIGN: We use
d immunohistochemical and immunoblotting techniques in a systematic st
udy of renal localization of four rabbit enzymes that represent three
major mammalian cytosolic glutathione S-transferase classes, alpha, pi
, and mu. RESULTS: The two alpha-class enzymes (rbGST alpha I, rbGST a
lpha II) were distributed discretely in kidney, ureter, and bladder, w
hile pi and mu were widely distributed in the renal system. Immunohist
ochemical localization in paraffin sections with antibodies specific f
or rbGST alpha I or rbGST alpha II demonstrated that no compartment of
the renal system contained both enzymes. Collecting ducts of the inne
r medulla and all epithelial cells of the kidney pelvis, ureter, and b
ladder contained rbGST alpha I. All cells lining proximal tubules cont
ained rbGST alpha II. No other compartment of the renal system exhibit
ed immunoreactivity with anti-rbGST alpha II. Antibody specific for pi
reacted with cells lining nephrons, ureter, and bladder and with endo
thelial cells throughout the renal system. Localization of pi was most
prominent in the collecting ducts of medulla and in the epithelial ce
lls lining the kidney pelvis, ureter, and bladder. As anti-mu did not
react in tissue sections, distribution of mu was determined by immunob
lotting. Immunoblots of cytosolic preparations from whole kidney, cort
ex, medulla, and epithelia of ureter, bladder, and kidney pelvis were
prepared and tested with each of the 4 antibodies. This second localiz
ation method confirmed the distribution data from tissue sections for
rbGST alpha I, rb GST alpha II, and pi; also, it demonstrated that the
staining observed in tissue was specifically for each enzyme. mu was
detected in all the renal cytosolic preparations except those from the
epithelium of the kidney pelvis. CONCLUSIONS: The discrete renal dist
ribution of rbGST alpha I and rbGST alpha II and their distinct cataly
tic activities with prostaglandin substrates suggest important roles f
or these enzymes in prostaglandin-dependent renal functions.