Department of Pathology, Children's Hospital Boston, Boston, MA Proteomics Center at Children's Hospital Boston, Boston, MA Center for Pancreatic Disease, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA.
Division of Gastroenterology and Hepatology, Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, MN.
Proteomics. 2013 May;13(9):1499-1512. doi: 10.1002/pmic.201200492.
Toxic compounds in tobacco, such as nicotine, may adversely affect pancreatic function. We aim to determine nicotine-induced protein alterations in pancreatic cells, thereby revealing links between nicotine exposure and pancreatic disease. We compared the proteomic alterations induced by nicotine treatment in cultured pancreatic cells (mouse, rat, and human stellate cells and human duct cells) using MS-based techniques, specifically SDS-PAGE (gel) coupled with LC-MS/MS and spectral counting. We identified thousands of proteins in pancreatic cells, hundreds of which were identified exclusively or in higher abundance in either nicotine-treated or untreated cells. Interspecies comparisons of stellate cell proteins revealed several differentially abundant proteins (in nicotine treated versus untreated cells) common among the three species. Proteins appearing in all nicotine-treated stellate cells include amyloid beta (A4), procollagen type VI alpha 1, integral membrane protein 2B, and toll-interacting protein. Proteins that were differentially expressed upon nicotine treatment across cell lines were enriched in certain pathways, including nicotinic acetylcholine receptor, cytokine, and integrin signaling. At this analytical depth, we conclude that similar pathways are affected by nicotine, but alterations at the protein level among stellate cells of different species vary. Further interrogation of such pathways will lead to insights into the potential effect of nicotine on pancreatic cells at the biomolecular level and the extension of this concept to the effect of nicotine on pancreatic disease.
烟草中的有毒化合物,如尼古丁,可能会对胰腺功能产生不良影响。我们旨在确定尼古丁在胰腺细胞中诱导的蛋白质改变,从而揭示尼古丁暴露与胰腺疾病之间的联系。我们使用基于 MS 的技术,特别是 SDS-PAGE(凝胶)与 LC-MS/MS 和光谱计数相结合,比较了尼古丁处理在培养的胰腺细胞(鼠、大鼠和人星状细胞和人胆管细胞)中诱导的蛋白质组学改变。我们在胰腺细胞中鉴定了数千种蛋白质,其中数百种蛋白质仅在尼古丁处理或未处理的细胞中或在更高丰度下被鉴定。星状细胞蛋白质的种间比较揭示了三种物种中共同存在的几种差异丰度蛋白(在尼古丁处理与未处理的细胞中)。出现在所有尼古丁处理的星状细胞中的蛋白质包括淀粉样β(A4)、原胶原蛋白 VI 型 α1、整合膜蛋白 2B 和 Toll 相互作用蛋白。在细胞系中经尼古丁处理后差异表达的蛋白质在某些途径中富集,包括烟碱型乙酰胆碱受体、细胞因子和整合素信号转导。在这种分析深度下,我们得出的结论是,相似的途径受到尼古丁的影响,但不同物种的星状细胞在蛋白质水平上的改变是不同的。进一步研究这些途径将有助于了解尼古丁对胰腺细胞在生物分子水平上的潜在影响,并将这一概念扩展到尼古丁对胰腺疾病的影响。