Increased oxidative DNA damage, inducible nitric oxide synthase, nuclear factor kB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac gastric adenocarcinoma

doi:10.3748/wjg.v10.i15.2232

中山醫學大學機構典藏 CSMUIR > 醫學院 > 生化微生物免疫研究所 > 期刊論文 > Item 310902500/10813

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/10813

Title:	Increased oxidative DNA damage, inducible nitric oxide synthase, nuclear factor kB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac gastric adenocarcinoma
Authors:	Chang, Chi-Sen Chen, Wei-Na Wu, Cheng-Chung Wang, Chau-Jong Lin, Hui-Hsuan
Contributors:	中山醫學大學
Date:	2004
Issue Date:	2015-05-15T04:55:37Z (UTC)
Abstract:	AIM: Several epidemiological studies have demonstrated a close association between Helicobacter pylori (H Pylori) infection and non-cardiac carcinoma of the stomach. H Pylori infection induces active inflammation with neutrophilic infiltrations as well as production of oxygen free radicals that can cause DNA damage. The DNA damage induced by oxygen free radicals could have very harmful consequences, leading to gene modifications that are potentially mutagenic and/or carcinogenic. The aims of the present study were to assess the effect of H Pylori infection on the expression of inducible nitric oxidative synthase (iNOS) and the production of 8-hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury in human gastric mucosa with and without tumor lesions, and to assess the possible factors affecting cell death signaling due to oxidative DNA damage. METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens were obtained from surgical resection. We determined the level of 8-OHdG formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death signaling [including nuclear factor-kB(NFkB), MEKK-1, Caspase 3, B Cell lymphomal leukemia-2 (Bcl-2), inhibitor of apoptosis protein (IAP ) and myeloid cell leukemia-1 (Mcl-1)] by Western-blot assay. RESULTS: The concentrations of 8-OHdG, iNOS, NFkB, Mcl-1 and IAP were significantly higher in cancer tissues than in adjacent non-cancer tissues. In addition, significantly higher concentrations of 8-OHdG, iNOS, NFkB, Mcl-1 and IAP were detected in patients infected with H Pylori compared with patients who were not infected with H Pylori. Furthermore, 8-OHdG, iNOS, NFkB, Mcl-1 and IAP concentrations were significantly higher in stage 3 and 4 patients than in stage 1 and 2 patients. CONCLUSION: Chronic H Pylori infection induces iNOS expression and subsequent DNA damage as well as enhances anti-apoptosis signal transduction. This sequence of events supports the hypothesis that oxygen-free radical-mediated damage due to H Pylori plays a pivotal role in the development of gastric carcinoma in patients with chronic gastritis. Chang CS, Chen WN, Lin HH, Wu CC, Wang CJ. Increased oxidative DNA damage, inducible nitric oxide synthase, nuclear factor kB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac gastric adenocarcinoma. World J Gastroenterol 2004; 10(15): 2232-2240 http://www.wjgnet.com/1007-9327/10/2232.asp
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/10813 http://dx.doi.org/10.3748/wjg.v10.i15.2232
Relation:	World J Gastroenterol 2004 August 1;10(15):2232-2240
Appears in Collections:	[生化微生物免疫研究所] 期刊論文

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