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

Associations between human liver and kidney cadmium content and immunochemically detected CYP4A11 apoprotein
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DOI:
10.1016/s0006-2952(01)00905-4
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发表时间:
2002-02-15
影响因子:
5.8
通讯作者:
Reilly, PEB
Reilly, PEB
中科院分区:
医学2区
文献类型:
--
作者:
Baker, JR;Satarug, S;Reilly, PEB

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本研究采用高度特异性的抗肽抗体,通过Western印迹法检测镉对人肝脏和肾脏中CYP 4A 11载脂蛋白的潜在影响。肝和肾皮质样品是37个个体(26个雄性和11个雌性)的尸检标本,其年龄范围从3至89岁。他们都是白人,在工作场所没有接触过镉。在慢性肝炎样本和显示脂肪变化的肝脏样本中发现CYP 4A 11载脂蛋白水平降低。与此相反,增加CYP 4A 11载脂蛋白水平被发现在肝脏样品中具有较高的镉含量相比,较低的镉含量的样品。与男性供体相比,女性供体的肝脏样本中也发现CYP 4A 11水平升高;差异可归因于女性肝脏镉负荷较高。与肝脏不同,在高镉含量的肾皮质样品中观察到较低的CYP 4A 11水平。本文提出,肝脏和肾脏样品的绝对镉负荷之间的差异可能是这两种组织中CYP 4A 11表达模式不同的原因。此外,由于镉暴露可能与血压控制紊乱有关,值得注意的是,肾皮质中花生四烯酸羟基和环氧代谢物的CYP 4A 11依赖性产生改变与血压控制改变之间可能存在关系。我们的发现提供了这些观察之间的可能联系。(C)2002年爱思唯尔科技有限公司All rights reserved.
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.