Aldehydes release zinc from proteins. A pathway from oxidative stress/lipid peroxidation to cellular functions of zinc
Aldehydes release zinc from proteins. A pathway from oxidative stress/lipid peroxidation to cellular functions of zinc
复制标题
DOI：
10.1111/j.1742-4658.2006.05428.x
复制
发表时间：
2006-09-01
期刊：
影响因子：
5.4
通讯作者：
Maret, Wolfgang
中科院分区：
文献类型：
--
作者：
Hao, Qiang;Maret, Wolfgang
氧化应激、脂质过氧化、高血糖诱导的糖基化和环境暴露增加了细胞中醛的浓度。醛类分子作用的一个新方面，例如乙醛和丙烯醛，是它们与蛋白质中锌位点的半胱氨酸配体的反应和伴随的锌释放。化学计量量的丙烯醛从金属硫蛋白和醇脱氢酶等蛋白质中的锌-硫酸盐配位释放锌。醛类化合物还能在培养的人肝癌（HepG2）细胞内释放锌，并干扰锌依赖的信号传导过程，如基因表达和磷酸化。因此乙醛和丙烯醛均诱导金属硫蛋白的表达，并以锌依赖的方式调节蛋白酪氨酸磷酸酶的活性。由于细胞锌的可用性的微小变化具有强大的影响，锌的释放是一种放大机制，可以解释醛的许多生物效应。醛类化合物的锌释放活性与细胞锌、内源性和外源性醛类化合物的功能以及氧化还原应激之间的关系，具有病理生化和毒理学机制的意义。
Oxidative stress, lipid peroxidation, hyperglycemia-induced glycations and environmental exposures increase the cellular concentrations of aldehydes. A novel aspect of the molecular actions of aldehydes, e.g. acetaldehyde and acrolein, is their reaction with the cysteine ligands of zinc sites in proteins and concomitant zinc release. Stoichiometric amounts of acrolein release zinc from zinc-thiolate coordination sites in proteins such as metallothionein and alcohol dehydrogenase. Aldehydes also release zinc intracellularly in cultured human hepatoma (HepG2) cells and interfere with zinc-dependent signaling processes such as gene expression and phosphorylation. Thus both acetaldehyde and acrolein induce the expression of metallothionein and modulate protein tyrosine phosphatase activity in a zinc-dependent way. Since minute changes in the availability of cellular zinc have potent effects, zinc release is a mechanism of amplification that may account for many of the biological effects of aldehydes. The zinc-releasing activity of aldehydes establishes relationships among cellular zinc, the functions of endogenous and xenobiotic aldehydes, and redox stress, with implications for pathobiochemical and toxicologic mechanisms.