Identification of S-nitrosylated proteins after chronic exposure of colon epithelial cells to deoxycholate
Identification of S-nitrosylated proteins after chronic exposure of colon epithelial cells to deoxycholate
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DOI：
10.1002/pmic.200500240
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发表时间：
2006-03-01
期刊：
影响因子：
3.4
通讯作者：
Payne, CM
中科院分区：
文献类型：
--
作者：
Dall'Agnol, M;Bernstein, C;Payne, CM
细胞凋亡抵抗，一种有利于基因组不稳定性的条件，与结直肠癌的高风险相关。脱氧胆酸盐（DOC）是一种疏水性胆汁盐，在结肠癌患者中以高浓度存在，并在培养的结肠细胞和离体结肠活检中诱导细胞凋亡。我们以前表明，结肠癌细胞慢性暴露于浓度增加的DOC导致细胞凋亡抗性，所提出的机制涉及氧化/亚硝化应激。一氧化氮（NO）是一种重要的信号分子，在多种生理和病理生理状态下调节细胞功能。在某种程度上，NO通过靶巯基的S-亚硝基化来发挥其作用，并且几种蛋白质通过这种PTM来调节，包括凋亡的主要效应物半胱天冬酶。在此，我们对DOC诱导的结肠癌耐药细胞系HCT-116 RC进行了蛋白质组学研究。将其S-亚硝基化蛋白质谱与未暴露于DOC的对照细胞系进行比较。在HCT-116 RC细胞系中鉴定了18个差异S-亚硝基化蛋白，其中14个是以前未报道的S-亚硝基化的新靶点。这些蛋白质包括细胞骨架和信号蛋白、代谢酶、分子伴侣以及氧化还原和分化相关蛋白。这些结果拓宽了我们对潜在信号转导途径的认识，这些途径可能导致新的生物标志物和治疗靶点的开发。
Apoptosis resistance, a condition favoring genomic instability, is associated with higher risk of colorectal cancer. Deoxycholate (DOC) is a hydrophobic bile salt found in high concentrations in colon cancer patients, and induces apoptosis in cultured colonic cells and ex vivo in colonic biopsies. We showed previously that the chronic exposure of colon cancer cells to increasing concentrations of DOC leads to apoptosis resistance, and the suggested mechanism involves oxidative/nitrosative stress. Nitric oxide (NO) is a key signaling molecule that regulates cell function in a variety of physiologic and pathophysiologic states. In part, NO exerts its actions by S-nitrosylation of target thiols, and several proteins are regulated through this PTM, including the caspases, the main effectors of apoptosis. Here, we performed a proteomics study in the DOC-induced apoptosis-resistant colon cell line, HCT-116RC. Its profile of S-nitrosylated proteins was compared to a control cell line not exposed to DOC. Eighteen differentially S-nitrosylated proteins were identified in the HCT-116RC cell line, 14 of these are novel targets of S-nitrosylation not previously reported. These proteins include cytoskeletal and signaling proteins, metabolic enzymes, chaperones, and redox- and differentiation-related proteins. These results broaden our knowledge of potential signal transduction pathways that may lead to the development of new biomarkers and therapy targets.