Tsaytler Pavel A, C O'Flaherty Martina, Sakharov Dmitri V, Krijgsveld Jeroen, Egmond Maarten R
Department of Membrane Enzymology, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
J Proteome Res. 2008 Sep;7(9):3868-78. doi: 10.1021/pr800189q. Epub 2008 Jul 25.
Oxidative stress induced in tumor cells undergoing photodynamic treatment (PDT) leads to extensive modification of many proteins in these cells. Protein oxidation mainly gives rise to formation of carbonyls and oxidized thiols. The immediate targets of PDT-induced protein oxidation in A431 tumor cells have been identified using a proteomic approach involving selective biotinylation, affinity purification and mass spectrometric identification of modified proteins. In all, 314 proteins were shown to undergo PDT-mediated oxidative modifications. While abundant structural proteins and chaperones represented a significant fraction of the carbonylated proteins, labeling of proteins containing oxidized thiols allowed identification of many proteins at low abundance and those involved in signaling and redox homeostasis. On the basis of the identification of these proteins, several likely mechanisms of PDT-induced triggering of apoptosis were put forward. This may not only lead to a further understanding of the complex network of cellular responses to oxidative stress, but it may also help in detailed targeting of photodynamic treatment applied to cancer.
接受光动力治疗（PDT）的肿瘤细胞中诱导产生的氧化应激会导致这些细胞内许多蛋白质发生广泛修饰。蛋白质氧化主要导致羰基和氧化型硫醇的形成。利用一种蛋白质组学方法，通过对修饰蛋白质进行选择性生物素化、亲和纯化和质谱鉴定，已确定了A431肿瘤细胞中PDT诱导的蛋白质氧化的直接靶点。总共314种蛋白质被证明会发生PDT介导的氧化修饰。虽然丰富的结构蛋白和伴侣蛋白占羰基化蛋白质的很大一部分，但对含氧化型硫醇蛋白质的标记使得能够鉴定出许多低丰度蛋白质以及参与信号传导和氧化还原稳态的蛋白质。基于这些蛋白质的鉴定结果，提出了几种PDT诱导细胞凋亡触发的可能机制。这不仅可能有助于进一步理解细胞对氧化应激的复杂反应网络，还可能有助于细化光动力治疗在癌症治疗中的靶向应用。
