title: Clinical proteomics identifies potential biomarkers in Helicobacter pylori for gastrointestinal diseases.
abstract: The development of gastrointestinal diseases has been found to be associated with Helicobacter pylori (H. pylori) infection and various biochemical stresses in stomach and intestine. These stresses, such as oxidative, osmotic and acid stresses, may bring about bi-directional effects on both hosts and H. pylori, leading to changes of protein expression in their proteomes. Therefore, proteins differentially expressed in H. pylori under various stresses not only reflect gastrointestinal environment but also provide useful biomarkers for disease diagnosis and prognosis. In this regard, proteomic technology is an ideal tool to identify potential biomarkers as it can systematically monitor proteins and protein variation on a large scale of cell's translational landscape, permitting in-depth analyses of host and pathogen interactions. By performing two-dimensional polyacrylamide gel electrophoresis (2-DE) followed by liquid chromatography-nanoESI-mass spectrometry (nanoLC-MS/MS), we have successfully pinpointed alkylhydroperoxide reductase (AhpC), neutrophil-activating protein and non-heme iron-binding ferritin as three prospective biomarkers showing up-regulation in H. pylori under oxidative, osmotic and acid stresses, respectively. Further biochemical characterization reveals that various environmental stresses can induce protein structure change and functional conversion in the identified biomarkers. Especially salient is the antioxidant enzyme AhpC, an abundant antioxidant protein present in H. pylori. It switches from a peroxide reductase of low-molecular-weight (LMW) oligomers to a molecular chaperone of high-molecular-weight (HMW) complexes under oxidative stress. Different seropositivy responses against LMW or HMW AhpC in H. pylori-infected patients faithfully match the disease progression from disease-free healthy persons to patients with gastric ulcer and cancer. These results has established AhpC of H. pylori as a promising diagnostic marker for gastrointestinal maladies, and highlight the utility of clinical proteomics for identifying disease biomarkers that can be uniquely applied to disease-oriented translational medicine.
authors.affiliation: Chun-Hao Huang, Shyh-Horng Chiou, Quantitative Proteomics Center and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Chun-Hao Huang, Shyh-Horng Chiou, Quantitative Proteomics Center and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Shyh-Horng
authors.initials: SH
authors.lastname: Chiou
mesh_terms: D000143:Acids / Q000737:chemistry; D001426:Bacterial Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004777:Environment; D005293:Ferritins / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000382:microbiology*; D016481:Helicobacter Infections / Q000175:diagnosis / Q000382:microbiology*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D009995:Osmosis; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000143:Acids; D001426:Bacterial Proteins; D015415:Biomarkers; C092412:neutrophil-activating protein A, Helicobacter pylori; D005293:Ferritins; D054464:Peroxiredoxins
keywords: Alkylhydroperoxide reductase; Biomarker; Gastric cancer; Gastric ulcer; Gastritis; Helicobacter pylori; Neutrophil-activating protein; Non-heme iron-binding ferritin; Proteomics