Grimsrud Paul A, Xie Hongwei, Griffin Timothy J, Bernlohr David A
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Biol Chem. 2008 Aug 8;283(32):21837-41. doi: 10.1074/jbc.R700019200. Epub 2008 Apr 29.
The term "oxidative stress" links the production of reactive oxygen species to a variety of metabolic outcomes, including insulin resistance, immune dysfunction, and inflammation. Antioxidant defense systems down-regulated due to disease and/or aging result in oxidatively modified DNA, carbohydrates, proteins, and lipids. Increased production of hydroxyl radical leads to the formation of lipid hydroperoxides that produce a family of alpha,beta-unsaturated aldehydes. Such reactive aldehydes are subject to Michael addition reactions with the side chains of lysine, histidine, and cysteine residues, referred to as "protein carbonylation." Although not widely appreciated, reactive lipids can accumulate to high levels in cells, resulting in extensive protein modification leading to either loss or gain of function. The use of mass spectrometric methods to identify the site and extent of protein carbonylation on a proteome-wide scale has expanded our view of how oxidative stress can regulate cellular processes.
术语“氧化应激”将活性氧的产生与多种代谢结果联系起来，包括胰岛素抵抗、免疫功能障碍和炎症。由于疾病和/或衰老导致抗氧化防御系统下调，会导致DNA、碳水化合物、蛋白质和脂质发生氧化修饰。羟自由基的产生增加会导致脂质氢过氧化物的形成，进而产生一系列α,β-不饱和醛。这些活性醛会与赖氨酸、组氨酸和半胱氨酸残基的侧链发生迈克尔加成反应，即“蛋白质羰基化”。尽管尚未得到广泛认识，但活性脂质可在细胞中大量积累，导致广泛的蛋白质修饰，从而导致功能丧失或获得。使用质谱方法在蛋白质组范围内鉴定蛋白质羰基化的位点和程度，拓宽了我们对氧化应激如何调节细胞过程的认识。
