Associations between human liver and kidney cadmium content and immunochemically detected CYP4A11 apoprotein

被引:21
作者
Baker, JR
Satarug, S
Urbenjapol, S
Edwards, RJ
Williams, DJ
Moore, MR
Reilly, PEB
机构
[1] Natl Res Ctr Environm Toxicol, Brisbane, Qld 4108, Australia
[2] Imperial Coll Sch Med, Clin Pharmacol Sect, London, England
[3] Queensland Hlth Sci Serv, John Tonge Ctr Forens Pathol, Brisbane, Qld, Australia
[4] Univ Queensland, Dept Biochem, Brisbane, Qld 4072, Australia
基金
英国医学研究理事会;
关键词
human autopsy; cadmium; cytochrome P450; fatty acid; vasoactive metabolites; blood pressure; hypertension;
D O I
10.1016/S0006-2952(01)00905-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mates and I I 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. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:693 / 696
页数:4
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