Document Detail


Epithelial cell expression of BCL-2 family proteins predicts mechanisms that regulate Helicobacter pylori-induced pathology in the mouse stomach.
MedLine Citation:
PMID:  18779780     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Corpus-predominant infection with Helicobacter pylori (HP) results in the activation of programmed cell death pathways in surface, parietal, and chief cells. At present, mechanisms that regulate these pathways to result in HP-associated pathology are not fully understood. Because it is not known which survival and death pathways are present in gastric epithelial cells, we used an antibody panel to evaluate the expression of BCL-2 family prosurvival proteins or multi-Bcl-2 homology (BH)-domains (group 1) or BH3-only (group-2) proapoptotic proteins in the stomachs of uninfected or HP-infected C57BL/6 mice. This strategy identified BCL-2, BAK, and BAD as the major prosurvival and proapoptotic proteins, in surface cells and BAD as the only BCL-2 family protein expressed in parietal cells. Chief cells express altogether different effectors, including BCL-X(L)/BCL-2, for survival but have no constitutively expressed proapoptotic proteins. In model chief cells, however, the group 1 proapoptotic protein BCL-X(S) was expressed after exposure to proinflammatory cytokines concomitant with reduced viability, demonstrating that chief cells can transcriptionally regulate the induction of proapoptotic proteins to execute apoptosis. During HP infection, no additional BCL-2 family proteins were expressed in epithelial cells, whereas those present either remained unchanged or were reduced as cell deletion occurred over time. Additional studies demonstrated that the posttranslational regulation of BAD in surface and parietal cells was negatively affected by HP infection, a result that may be directly related to an increase in apoptosis during infection. Thus, gastric epithelial cells express cell-specific prosurvival and proapoptotic pathways. From the results presented here, mechanisms that regulate HP-related changes in the survival and death profile of gastric epithelial cells can be predicted and then tested, with the ultimate goal of elucidating important therapeutic targets to inhibit the progression of HP-related pathology in the stomach.
Authors:
Susan J Hagen; David X Yang; Kimihito Tashima; Nancy S Taylor; James G Fox
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-09-08
Journal Detail:
Title:  Laboratory investigation; a journal of technical methods and pathology     Volume:  88     ISSN:  1530-0307     ISO Abbreviation:  Lab. Invest.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-28     Completed Date:  2008-12-16     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0376617     Medline TA:  Lab Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1227-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology*
Cells, Cultured
Chief Cells, Gastric / metabolism*
Disease Models, Animal
Female
Helicobacter Infections / physiopathology*
Helicobacter pylori*
Mice
Parietal Cells, Gastric / metabolism*
Protein Processing, Post-Translational
Stomach Diseases / microbiology,  physiopathology*
bcl-Associated Death Protein / metabolism
bcl-X Protein / metabolism
Grant Support
ID/Acronym/Agency:
P30 DK-34854/DK/NIDDK NIH HHS; P30 DK034854/DK/NIDDK NIH HHS; R01 AI/RR-37750/AI/NIAID NIH HHS; R01 AI037750/AI/NIAID NIH HHS; R01 AI037750-13/AI/NIAID NIH HHS; R01 CA-67463/CA/NCI NIH HHS; R01 DK-15681/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Bad protein, mouse; 0/bcl-Associated Death Protein; 0/bcl-X Protein
Comments/Corrections

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