Phenobarbital-inducible aldehyde dehydrogenase in the rat. cDNA sequence and regulation of the mRNA by phenobarbital in responsive rats.
In the rat, a cytosolic isozyme of aldehyde dehydrogenase, designated ALDH-PB, can be induced in the liver by administration of phenobarbital (PB). ALDH-PB activity and mRNA are induced in Long-Evans rats that possess a responsive (R) allele but are not induced in homozygous nonresponsive rats (rr), although the rr genotype is competent to induce other PB-responsive mRNAs. ALDH-PB mRNA is expressed in the basal state (without PB administration) in hepatic tissue in both RR and rr genotypes. We report the complete nucleotide sequence of the rat ALDH-PB mRNA. The protein encoded by the ALDH-PB mRNA is 501 amino acids in length and has a predicted molecular mass of 54,540 daltons. The amino acid sequence predicted from the mRNA demonstrates a strong conservation between the rat ALDH-PB and the human cytosolic aldehyde dehydrogenase hALDH-1. We demonstrate the ALDH-PB, cytochrome P-450b, cytochrome P-450e, and glutathione S-transferase Ya subunit mRNA levels in the liver are altered noncoordinately by administration of PB in RR and rr genotypes. The strikingly different responses to PB administration between the various mRNA species in each of the genotypes suggest that the regulation of specific gene expression by PB may involve multiple pathways.
Dunn
T J
TJ
Department of Oncology, Medical School, University of Wisconsin, Madison 53706.
Koleske
A J
AJ
Lindahl
R
R
Pitot
H C
HC
D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000302:isolation & purification*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000302:isolation & purification; D008099:Liver / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D010634:Phenobarbital / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011920:Rats, Inbred WF
D007527:Isoenzymes; D012333:RNA, Messenger; D004247:DNA; D000444:Aldehyde Dehydrogenase; D010634:Phenobarbital