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Alkylhydroperoxide reductase of Helicobacter pylori as a biomarker for gastric patients with different pathological manifestations |
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| Authors: | Huang Chun-Hao Chuang Ming-Hong Lo Wan-Lin Wu Ming-Shiang Wu Yuan-Heng Wu Deng-Chyang Chiou Shyh-Horng |
| Affiliation: | a Graduate Institute of Medicine, Center for Research Resources and Development, and Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan b Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan c Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan d Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan e Division of Gastroenterology, Department of Internal Medicine, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan f Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan |
| Abstract: | The development of various gastrointestinal diseases was suggested to be associated with chronic inflammation as a consequence of Helicobacter pylori (H. pylori) infection. Our previous studies showed that an antioxidant protein alkylhydroperoxide reductase (AhpC) is an abundant and important antioxidant protein present in H. pylori. In this study we have explored the potential of utilizing antibodies to AhpC for detection of patients who are at high risks of evolving into severe outcomes of gastric malignancies after H. pylori infection. The correlation between AhpC and extents of inflammatory damage in tissues was demonstrated by immunoblotting assays and endoscopic examinations. Oxidative stress-induced high-molecular-weight (HMW) AhpC with chaperone activity in vivo was further investigated by co-immunoprecipitation, 2-dimensional gel electrophoresis (2-DE) followed by nano-liquid chromatography coupled tandem mass spectrometry (nanoLC-MS/MS). We found AhpC was consistently expressed in higher amounts in H. pylori strains isolated from patients with gastric cancer (GC) than gastritis (GA). Immunological analysis of seropositivity for AhpC indicated that positive diagnostic rates for H. pylori-infected patients with GA, gastric ulcer (GU) and GC were 68% (15/22), 100% (50/50) and 100% (50/50), respectively. In great contrast to low-molecular-weight (LMW) AhpC, HMW AhpC with chaperone function was found to distribute inside of H. pylori cells. We also found that LMW forms of AhpC were recognized by serum antibodies from GA patients whereas HMW forms of AhpC reacted mainly with those from GU and GC patients. Based on the significant difference between AhpC isolated from strains of GC and GA, it is conceivable that AhpC of H. pylori may prove to be useful as a prognostic or diagnostic protein marker to monitor varied clinical manifestations of gastrointestinal patients infected with H. pylori. |
| Keywords: | Helicobacter pylori Alkylhydroperoxide reductase Oxidative stress Gastritis Gastric ulcer Gastric cancer |
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