Department of Oral Biochemistry, Dental Science Research Institute and the Brain Korea 21 Project, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Hwasun, Korea.
Mol Cells. 2013 Jun;35(6):533-42. doi: 10.1007/s10059-013-0058-1. Epub 2013 May 14.
Oxidative stress promotes damage to cellular proteins, lipids, membranes and DNA, and plays a key role in the development of cancer. Reactive oxygen species disrupt redox homeostasis and promote tumor formation by initiating aberrant activation of signaling pathways that lead to tumorigenesis. We used shotgun proteomics to identify proteins containing oxidation-sensitive cysteines in tissue specimens from colorectal cancer patients. We then compared the patterns of cysteine oxidation in the membrane fractions between the tumor and non-tumor tissues. Using nano-UPLC-MS(E) proteomics, we identified 31 proteins containing 37 oxidation-sensitive cysteines. These proteins were observed with IAM-binding cysteines in non-tumoral region more than tumoral region of CRC patients. Then using the Ingenuity pathway program, we evaluated the cellular canonical networks connecting those proteins. Within the networks, proteins with multiple connections were related with organ morphology, cellular metabolism, and various disorders. We have thus identified networks of proteins whose redox status is altered by oxidative stress, perhaps leading to changes in cellular functionality that promotes tumorigenesis.
氧化应激会促进细胞蛋白质、脂质、膜和 DNA 的损伤，并在癌症的发展中起关键作用。活性氧会破坏氧化还原平衡，并通过启动导致肿瘤发生的信号通路的异常激活来促进肿瘤形成。我们使用鸟枪法蛋白质组学鉴定了来自结直肠癌患者组织标本中含有氧化敏感半胱氨酸的蛋白质。然后，我们比较了肿瘤和非肿瘤组织中膜部分的半胱氨酸氧化模式。使用纳升超高效液相色谱-串联质谱（E）蛋白质组学，我们鉴定了 31 种含有 37 个氧化敏感半胱氨酸的蛋白质。这些蛋白质在 CRC 患者的非肿瘤区域比肿瘤区域观察到更多的 IAM 结合半胱氨酸。然后，我们使用Ingenuity通路程序评估了连接这些蛋白质的细胞典型网络。在网络中，具有多个连接的蛋白质与器官形态、细胞代谢和各种疾病有关。因此，我们已经鉴定出了由氧化应激改变其氧化还原状态的蛋白质网络，这些改变可能导致促进肿瘤发生的细胞功能变化。
