Baker Jason R, Satarug Soisungwan, Edwards Robert J, Moore Michael R, Williams David J, Reilly Paul E B
National Research Center for Environmental Toxicology, University of Queensland, 39 Kessels Road, Coopers Plains, Qld. 4108, Brisbane, Australia.
Toxicol Lett. 2003 Jan 31;137(1-2):85-93. doi: 10.1016/s0378-4274(02)00382-x.
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.
本文研究了非工作场所镉(Cd)暴露、细胞色素P450表达与高血压之间可能存在的联系。我们展示了关于肝肾镉负荷与细胞色素P450同工酶4A11丰度之间关系的调查结果。我们的数据显示非工作场所镉暴露与肝和肾皮质中细胞色素P450 4A11丰度变化之间存在关联。在肝脏中,免疫化学可检测到的细胞色素P450 4A11水平与组织镉含量呈正相关,而相比之下,细胞色素P450 4A11丰度与肾脏镉负荷呈负相关。这些差异很可能与组织的不同镉负荷有关。这些观察结果表明镉有可能作为肾皮质中细胞色素P450 4A11表达的介质,并表明肾脏镉含量的升高可能通过改变这种特定同工酶的表达而参与高血压的发生。文中简要讨论了镉可能改变细胞色素P450 4A11表达的潜在机制。