Reactions of the Zn Proteome with Cd2+ and Other Xenobiotics: Trafficking and Toxicity

详细信息    查看全文

• 作者：David H. Petering
• 刊名：Chemical Research in Toxicology
• 出版年：2017
• 出版时间：January 17, 2017
• 年：2017
• 卷：30
• 期：1
• 页码：189-202
• 全文大小：561K
• ISSN：1520-5010

文摘

Understanding the molecular basis of inorganic chemical toxicity has lagged behind the proliferation of detailed mechanisms that explain the biochemical toxicology of many organic xenobiotics. In this perspective, general barriers to explicating the bioinorganic chemistry of toxic metals are considered, followed by a detailed examination of these issues in relation to the toxicology of Cd²⁺. The hypothesis is evaluated that Cd²⁺ damages cells by replacing Zn²⁺ in key Zn proteins. An emerging methodology to assess the speciation of metals among cell proteins is described. Then, a more general hypothesis is suggested, namely, that the Zn proteome is also the toxicological target of other metals such as Pb²⁺ as well as NO and reactive oxygen species. The latter may damage cells by altering the structure and function of Zn²⁺ binding sites that include thiol ligands. In the process, labilized Zn²⁺ may also perturb cell biochemistry. Lastly, reactions of metal chelating ligands with the Zn proteome, including formation of ligand–Zn protein adducts, provide other potential avenues of biochemical toxicity.