Associations between human liver and kidney cadmium content and immunochemically detected CYP4A11 apoprotein.
This present study was undertaken to assess potential effects of cadmium on CYP4A11 apoprotein in human liver and kidney as detected by Western blotting using a highly specific anti-peptide antibody. Liver and kidney cortex samples were autopsy specimens of 37 individuals (26 males and 11 females) whose ages ranged from 3 to 89 years. All were Caucasians who had not been exposed to cadmium in the workplace. Reduced CYP4A11 apoprotein levels were found in chronic hepatitis samples and in liver samples showing fatty changes. In contrast, increased CYP4A11 apoprotein levels were found in liver samples having higher cadmium content compared to the lower cadmium content samples. Increased CYP4A11 levels were also found in liver samples from female donors, compared to male donors; the difference being attributable to higher female liver cadmium burden. In distinction to liver, lowered CYP4A11 levels were seen in the kidney cortex samples which have high cadmium content. It is proposed here that the difference between the absolute cadmium burden of the liver and kidney samples may be responsible for the different patterns of expression of CYP4A11 in these two tissues. Further, since cadmium exposure may be associated with derangement in blood pressure control, it is interesting to note the possible relationship between altered CYP4A11-dependent production of arachidonic acid hydroxy and epoxy metabolites in kidney cortex and altered control of blood pressure. Our findings provide a possible link between these observations.
Baker
Jason R
JR
National Research Centre for Environmental Toxicology, 39 Kessels Road, Coopers Plains, Brisbane 4108, Queensland, Australia. s274705@student.uq.edu.au
Satarug
Soisungwan
S
Urbenjapol
Supanee
S
Edwards
Robert J
RJ
Williams
David J
DJ
Moore
Michael R
MR
Reilly
Paul E B
PE
D000293:Adolescent; D000328:Adult; D002104:Cadmium / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D005260:Female; D006801:Humans; D007120:Immunochemistry; D007668:Kidney / Q000737:chemistry*; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000032:analysis*; D012907:Smoking / Q000378:metabolism
D002104:Cadmium; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A