Differential induction of glutathione S-transferase subunits by spironolactone in rat liver, jejunum and colon.
The effect of spironolactone pretreatment on glutathione S-transferase activity and on the relative content of the principal subunits (Ya, Yc, Yb1, Yb2 and Yp or 1, 2, 3, 4 and 7 respectively) was studied in rat liver, jejunum and colon. Male Wistar rats were injected with spironolactone i.p. at daily doses of 50, 100 and 200 micromol/kg body wt for 3 consecutive days. Glutathione S-transferase activities were assayed using 1-chloro-2,4-dinitrobenzene as substrate. Changes in subunit composition were evaluated by Western blot analysis in rats treated with the highest dose of spironolactone. The results demonstrated a dose-dependent increase in enzyme activity in liver, while in jejunum the three tested doses exhibited the same magnitude of induction. No significant difference in glutathione S-transferase activity was observed between control and treated rats for the colon. Immunoblot analysis revealed more Ya and Yp protein in liver (140 and 118% increase respectively) and jejunum (45 and 145% increase respectively) from treated rats. While Ya and Yp relative contents were similar in jejunum, the latter subunit slightly contributed to total GST in liver, even in SL-treated animals. The inducer produced no change in subunit composition in colon. In conclusion, spironolactone was able to increase glutathione S-transferase activity mainly by induction of Ya subunit in liver and Yp subunit in jejunal mucosa, without affecting colonic enzyme.
Catania
V A
VA
Instituto de Fisiología Experimental, CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, U.N.R., Rosario, Argentina.
Luquita
M G
MG
Sánchez Pozzi
E J
EJ
Mottino
A D
AD
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003106:Colon / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis*; D007583:Jejunum / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology*
D013148:Spironolactone; D005982:Glutathione Transferase