Potential for early involvement of CYP isoforms in aspects of human cadmium toxicity.
This paper investigates the possible link between non-workplace cadmium (Cd) exposure, cytochrome P450 expression and hypertension. We present results of our investigation into the relationships between liver and kidney Cd burdens and the abundance of the CYP isoform 4A11. Our data show associations between non-workplace Cd exposure and changes in the abundance of hepatic and renal cortical CYP4A11. In liver the levels of immunochemically detectable CYP4A11 were positively correlated with tissue Cd content while in contrast CYP4A11 abundance was inversely correlated with kidney Cd burden. These differences are most likely related to the different Cd burden of the tissues. These observations suggest the potential for involvement of Cd as a mediator of CYP4A11 expression in kidney cortex and indicate that elevations in kidney Cd content may be involved in hypertension via alteration of the expression of this particular isoform. Potential mechanisms by which Cd may alter CYP4A11 expression are discussed briefly.
Baker
Jason R
JR
National Research Center for Environmental Toxicology, University of Queensland, 39 Kessels Road, Coopers Plains, Qld. 4108, Brisbane, Australia. s374705@student.uq.edu.au
Satarug
Soisungwan
S
Edwards
Robert J
RJ
Moore
Michael R
MR
Williams
David J
DJ
Reilly
Paul E B
PE
D000293:Adolescent; D000328:Adult; D000368:Aged; D001822:Body Burden; D002104:Cadmium / Q000009:adverse effects* / Q000493:pharmacokinetics; D002105:Cadmium Poisoning / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000209:etiology; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008875:Middle Aged
D002104:Cadmium; D003577:Cytochrome P-450 Enzyme System; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A