tailieunhanh - Báo cáo khoa học: Aldehydes release zinc from proteins. A pathway from oxidative stress⁄lipid peroxidation to cellular functions of zinc

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, . acetaldehyde and acrolein, is their reaction with the cysteine ligands of zinc sites in proteins and concomitant zinc release. | ễFEBS Journal Aldehydes release zinc from proteins. A pathway from oxidative stress lipid peroxidation to cellular functions of zinc Qiang Hao and Wolfgang Maret Departments of Preventive Medicine Community Health and Anesthesiology The University of Texas MedicalBranch Galveston TX USA Keywords acetaldehyde acrolein metallothionein oxidative stress zinc Correspondence W. Maret Division of Human Nutrition Preventive Medicine and Community Health The University of Texas Medical Branch 700 Harborside Drive Galveston TX 77555 USA Fax 1 409 772 6287 Tel 1 409 772 4661 E-mail womaret@ Received 2 May 2006 revised 14 July 2006 accepted 20 July 2006 doi 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 . 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 metallothion-ein 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. The aldehyde group is the most reactive among the functional groups of .