The major alpha-class glutathione S-transferases of rabbit lung and liver. Primary sequences, expression, and regulation.
The complete primary structures of two distinct rabbit alpha-class glutathione S-transferase (GST) subunits, rbGST alpha I and rbGST alpha II, have been derived from cDNA sequences. Clones encoding rbGST alpha I were isolated from both hepatic and pulmonary cDNA libraries, whereas clones encoding rbGST alpha II were isolated only from the hepatic library. Immunochemical and peptide sequence data confirmed that rbGST alpha I corresponds to the 27-kDa alpha-class subunit purified from rabbit lung (Serabjit-Singh, C. J., and Bend, J. R. (1988) Arch. Bioch. Biophys. 267, 184-194). Expression of rbGST alpha II in liver but not in lung and expression of rbGST alpha I in both liver and lung was substantiated by Northern and immunochemical analyses. rbGST alpha I and rbGST alpha II are composed of 223 and 221 amino acids, respectively, and are 78% identical in amino acid sequence. Compared to published GST sequences, both proteins are most closely related to the human Ha subunit (greater than 80% identity). On the basis of sequence comparison and Northern and Southern analyses, we conclude that rbGST alpha I and rbGST alpha II are products of different genes that are independently regulated. Further, the regulatory elements of the alpha-class GST genes may be significantly different in the rabbit as compared to the rat, as evidenced by the lack of induction by phenobarbital of rabbit hepatic or pulmonary alpha-class GST subunits, enzymatic activity, or mRNA. This tissue- and species-dependent expression of the predominant class of cytosolic GST implies unique functions for each isozyme and may contribute to the differential susceptibility of tissues and animals to toxicants.
Department of Drug Metabolism, Glaxo Inc. Research Institute, Research Triangle Park, North Carolina.
S
S
Gardlik
R
R
Gasser
R M
RM
Philpot
C J
CJ
Serabjit-Singh
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D003429:Cross Reactions; D004247:DNA / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008168:Lung / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D010634:Phenobarbital / Q000494:pharmacology; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D012689:Sequence Homology, Nucleic Acid
D012333:RNA, Messenger; D004247:DNA; D005982:Glutathione Transferase; D010634:Phenobarbital