Apparent deficiency of metallothionein in the Wistar rat prostate.
The high affinity metal-binding protein metallothionein (MT) is thought to detoxify cadmium (Cd) but appears to be deficient in several known targets of Cd carcinogenesis. The rat ventral prostate (VP) was recently identified as one of these target tissues. The nature of the Cd-binding proteins in the prostate has not been well defined, and thus this study attempted to define the nature of these proteins in the Wistar rat. A Zn-, Cd-binding protein fraction in the low-molecular-weight range was seen by gel filtration in cytosol from either dorsal prostate (DP) or VP. These prostatic proteins eluted with a relative elution volume similar to that of authentic MT, and were extractable by heat treatment and sequential acetone precipitation, a technique originally developed for purification of MT. Preparations of such partially purified prostatic protein were further purified using a reverse-phase HPLC technique developed for MT isoform isolation. One form was detected from the VP while the DP displayed five separate forms, eluting in a range like that of the two isoforms of rat MT. However, on the basis of amino acid content, none of these prostatic forms were classifiable as MTs, due to the absence of cysteine, a very common amino acid in MT. Unlike MT which is devoid of aromatic amino acids, the prostatic proteins also contained significant amounts of tyrosine and phenylalanine. The prostatic proteins also contained much more glutamate than MT. Cadmium treatment, which is known to cause a marked induction of MT, did not alter levels of this protein in the prostate, while markedly increasing hepatic MT. The present results indicate that these low-molecular-weight Cd-, Zn-binding proteins present in the rat prostate are not MTs and provide a further correlation between MT deficiency and sensitivity to the carcinogenic effects of Cd.
Waalkes
M P
MP
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland 21701.
Perantoni
A
A
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002104:Cadmium / Q000378:metabolism* / Q000493:pharmacokinetics; D002352:Carrier Proteins / Q000032:analysis; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003600:Cytosol / Q000032:analysis; D008099:Liver / Q000032:analysis; D008297:Male; D008668:Metallothionein / Q000172:deficiency*; D008970:Molecular Weight; D011467:Prostate / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D015032:Zinc / Q000378:metabolism
D000596:Amino Acids; D002352:Carrier Proteins; D002104:Cadmium; D008668:Metallothionein; D015032:Zinc