Hao Qiang, Maret Wolfgang
Departments of Preventive Medicine & Community Health and Anesthesiology, The University of Texas Medical Branch, Galveston, TX, USA.
FEBS J. 2006 Sep;273(18):4300-10. doi: 10.1111/j.1742-4658.2006.05428.x. Epub 2006 Aug 23.
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.
氧化应激、脂质过氧化、高血糖诱导的糖基化以及环境暴露会增加细胞内醛类的浓度。醛类（如乙醛和丙烯醛）分子作用的一个新方面是它们与蛋白质中锌位点的半胱氨酸配体发生反应并伴随锌的释放。化学计量的丙烯醛会从金属硫蛋白和乙醇脱氢酶等蛋白质中的硫醇锌配位位点释放锌。醛类还会在培养的人肝癌（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，乙醛和丙烯醛都会诱导金属硫蛋白的表达，并以锌依赖的方式调节蛋白质酪氨酸磷酸酶的活性。由于细胞内锌可用性的微小变化会产生强大影响，锌释放是一种放大机制，可能解释了醛类的许多生物学效应。醛类的锌释放活性建立了细胞锌、内源性和外源性醛类的功能以及氧化还原应激之间的关系，对病理生物化学和毒理学机制具有重要意义。
