| Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: implications for gastric carcinogenesis. | |
| | |
MedLine Citation:
|
PMID: 15574757 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Oxidative stress is linked to carcinogenesis due to its ability to damage DNA. The human gastric pathogen Helicobacter pylori exerts much of its pathogenicity by inducing apoptosis and DNA damage in host gastric epithelial cells. Polyamines are abundant in epithelial cells, and when oxidized by the inducible spermine oxidase SMO(PAOh1) H(2)O(2) is generated. Here, we report that H. pylori up-regulates mRNA expression, promoter activity, and enzyme activity of SMO(PAOh1) in human gastric epithelial cells, resulting in DNA damage and apoptosis. H. pylori-induced H(2)O(2) generation and apoptosis in these cells was equally attenuated by an inhibitor of SMO(PAOh1), by catalase, and by transient transfection with small interfering RNA targeting SMO(PAOh1). Conversely, SMO(PAOh1) overexpression induced apoptosis to the same levels as caused by H. pylori. Importantly, in H. pylori-infected tissues, there was increased expression of SMO(PAOh1) in both human and mouse gastritis. Laser capture microdissection of human gastric epithelial cells demonstrated expression of SMO(PAOh1) that was significantly attenuated by H. pylori eradication. These results identify a pathway for oxidative stress-induced epithelial cell apoptosis and DNA damage due to SMO(PAOh1) activation by H. pylori that may contribute to the pathogenesis of the infection and development of gastric cancer. |
| | |
Authors:
|
Hangxiu Xu; Rupesh Chaturvedi; Yulan Cheng; Francoise I Bussiere; Mohammad Asim; Micheal D Yao; Darryn Potosky; Stephen J Meltzer; Juong G Rhee; Sung S Kim; Steven F Moss; Amy Hacker; Yanlin Wang; Robert A Casero; Keith T Wilson |
Related Documents
:
|
11549817 - Impact of helicobacter pylori virulence on the outcome of gastroduodenal diseases: less... 9845587 - Gastrin and the enterochromaffin-like cell: an acid update. 12214957 - The importance of confounding in observational before-and-after studies of road safety ... 15557597 - Downregulation of cxcr1 and cxcr2 expression on human neutrophils by helicobacter pylor... 21731497 - Interferon regulatory factor 8 regulates pathways for antigen presentation in myeloid c... 17315157 - Overexpressed raf-1 and phosphorylated cyclic adenosine 3'-5'-monophosphatate response ... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Cancer research Volume: 64 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 2004 Dec |
Date Detail:
|
Created Date: 2004-12-02 Completed Date: 2005-01-27 Revised Date: 2011-11-02 |
Medline Journal Info:
|
Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
|
Languages: eng Pagination: 8521-5 Citation Subset: IM |
Affiliation:
|
Department of Medicine, Division of Gastroenterology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Apoptosis
/
physiology* DNA Damage / physiology* Enzyme Induction Gastric Mucosa / enzymology, metabolism*, microbiology* Gene Expression Regulation, Enzymologic Gene Silencing Helicobacter Infections / enzymology, metabolism* Helicobacter pylori / metabolism* Humans Hydrogen Peroxide / metabolism Oxidation-Reduction Oxidative Stress Oxidoreductases Acting on CH-NH Group Donors / biosynthesis, genetics, metabolism Promoter Regions, Genetic RNA, Messenger / biosynthesis, genetics Spermine / metabolism* Stomach / enzymology, metabolism, microbiology Stomach Neoplasms / enzymology, metabolism, microbiology* |
| Grant Support | |
ID/Acronym/Agency:
|
CA01808/CA/NCI NIH HHS; CA51085/CA/NCI NIH HHS; CA77057/CA/NCI NIH HHS; CA85069/CA/NCI NIH HHS; CA95323/CA/NCI NIH HHS; CA98454/CA/NCI NIH HHS; DK53620/DK/NIDDK NIH HHS; DK63626/DK/NIDDK NIH HHS; RR17695/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/RNA, Messenger; 71-44-3/Spermine; 7722-84-1/Hydrogen Peroxide; EC 1.5.-/Oxidoreductases Acting on CH-NH Group Donors; EC 1.5.3.-/polyamine oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Analysis of diepoxide-specific cyclic N-terminal globin adducts in mice and rats after inhalation ex...
Next Document: Defective DNA strand break repair after DNA damage in prostate cancer cells: implications for geneti...