Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2 and CYP2E1
Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2 and CYP2E1
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DOI：
10.1016/j.toxlet.2005.05.016
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发表时间：
2005-11-15
影响因子：
3.5
通讯作者：
Satarug, S
中科院分区：
文献类型：
--
作者：
Baker, JR;Edwards, RJ;Satarug, S
本研究利用免疫印迹法结合金属分析检测了金属毒素镉（Cd）和铅（Pb）的积累与细胞色素P450 4F2 （CYP4F2）、CYP2E1丰度以及锌和铜在肝脏和肾脏样本中的浓度之间的关系。尸检肝脏和肾脏皮层样本来自23名男性和8名女性，年龄在3-89岁之间。他们都是没有在工作场所接触过金属的白种人。肾皮质Cd平均负荷为17.4 μ g/g w.w.，是肝脏Cd平均负荷（1.1 μ g/g w.w.）的17倍。相比之下，肾皮质平均Ph负荷为0.09 μ g/g w.w.，比肝脏平均Pb负荷0.19 μ g/g w.w.低2倍，肾皮质样品平均Zn和Cu浓度分别比肝脏低67%和33%。肝脏和肾脏Cd负荷与供体年龄呈正相关，而肝脏和肾脏Ph负荷与供体年龄无关。在控制肝脏Cd负荷后，锌与年龄呈负相关（部分r = -0.39, P = 0.02），提示老年人肝脏锌水平降低。肝脏CYP2E1蛋白丰度与年龄调整后的Cd负荷呈正相关（部分r = 0.37, P = 0.02），肾脏CYP4172蛋白丰度与年龄调整后的Cd负荷呈正相关（部分r = 0.40, P = 0.02）。这些发现表明，Cd可能是肾脏CYP4172和肝脏CYP2E1的诱导剂，并且肾脏CYP4172表达的增加可能与Cd相关的肾小管功能障碍和高血压有关，涉及cyp4f2依赖性花生四烯酸代谢。2005爱思唯尔爱尔兰有限公司版权所有。
The present study examined accumulation of the metal toxins cadmium (Cd) and lead (Pb) in relation to the abundance of cytochrome P450 4F2 (CYP4F2), CYP2E1 and concentrations of zinc and copper in liver and kidney samples using immunoblotting coupled with metal analysis. The post mortem liver and kidney cortex samples were from 23 males and 8 females aged 3-89 years. All were Caucasians who had not been exposed to metals in the workplace. Average kidney cortex Cd load of 17.4 mu g/g w.w. was 17 times greater than average liver Cd load (1.1 mu g/g w.w.). In contrast, average kidney cortex Ph load of 0.09 mu g/g w.w. was two times lower than liver Pb load of 0.19 mu g/g w.w. Average Zn and Cu concentrations in the kidney cortex samples were 67% and 33% lower than those in the liver. Liver and kidney Cd loads, but not liver or kidney Ph loads, correlated positively with donors' age. After controlling for liver Cd load, an inverse correlation was seen between Zn and age (partial r = -0.39, P = 0.02), suggesting reduction in liver Zn levels in old age. Liver CYP2E1 protein abundance correlated with age-adjusted Cd load (partial r = 0.37, P = 0.02) whereas kidney CYP4172 protein abundance showed a positive correlation with age-adjusted Cd loads (partial r = 0.40, P = 0.02). These findings suggest that Cd may be an inducer of renal CYP4172 and hepatic CYP2E1 and that increased renal CYP4172 expression may implicate in Cd-linked renal tubular dysfunction and high blood pressure, involving CYP4F2-dependent arachidonic acid metabolism. (c) 2005 Elsevier Ireland Ltd. All rights reserved.