Identification of S-nitrosylated proteins after chronic exposure of colon epithelial cells to deoxycholate.
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.
Dall'Agnol
Monique
M
Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson, AZ, USA.
Bernstein
Carol
C
Bernstein
Harris
H
Garewal
Harinder
H
Payne
Claire M
CM
D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D003106:Colon / Q000033:anatomy & histology* / Q000187:drug effects; D003110:Colonic Neoplasms; D003840:Deoxycholic Acid / Q000494:pharmacology*; D003902:Detergents / Q000494:pharmacology*; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects; D009603:Nitroso Compounds / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D020543:Proteome / Q000032:analysis
D003902:Detergents; D009603:Nitroso Compounds; D011506:Proteins; D020543:Proteome; D003840:Deoxycholic Acid