Suppression of carbonic anhydrase III in rat liver by a dioxin-related toxic compound, coplanar polychlorinated biphenyl, 3, 3',4,4',5-pentachlorobiphenyl.
A coplanar polychlorinated biphenyl, 3,3',4,4',5-pentachlorobiphenyl (PenCB), significantly suppresses the expression of rat liver carbonic anhydrase III (CAIII), an enzyme which has recently been suggested to prevent from H(2)O(2)-inducible apoptosis. Marked changes in the CAIII levels of liver cytosol were observed in rats following doses of PenCB ranging from 0.5 to 25 mg/kg body weight and maximum suppression was observed at a dose of 10 mg/kg. Northern analysis revealed that the level of CAIII mRNA in rat liver was dramatically reduced by PenCB treatment while only weak suppression was observed in pair-fed controls. Two AU-rich elements, considered as a destabilizing signal of mRNA, were found in the 3'-untranslated region of CAIII sequenced after reverse transcription-PCR and 3'-rapid amplification of the cDNA end. Dramatic decrease of CAIII in rat liver by PenCB could account for the suppression of the defense system for oxidative stress.
Ikeda
M
M
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Ishii
Y
Y
Kato
H
H
Akazawa
D
D
Hatsumura
M
M
Ishida
T
T
Matsusue
K
K
Yamada
H
H
Oguri
K
K
D020413:3' Untranslated Regions; D000818:Animals; D015152:Blotting, Northern; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D003600:Cytosol / Q000201:enzymology; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015151:Immunoblotting; D008099:Liver / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020413:3' Untranslated Regions; D002257:Carbonic Anhydrase Inhibitors; D018076:DNA, Complementary; D011078:Polychlorinated Biphenyls; D017027:Protein Tyrosine Phosphatases; D002256:Carbonic Anhydrases; C023035:3,4,5,3',4'-pentachlorobiphenyl