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Helicobacter pylori activates μ‐calpain to cleave E‐cadherin in epithelial monolayers
Author(s) -
O'Connor Pamela M,
Lapointe Tamia K.,
Buret Andre G.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.320.9
Subject(s) - calpain , adherens junction , blot , cadherin , caga , helicobacter pylori , microbiology and biotechnology , proteases , chemistry , biology , cell , biochemistry , enzyme , virulence , genetics , gene
H.pylori (Hp) is a risk factor for gastritis, gastric ulcers, and adenocarcinoma. The ability of Hp to disrupt epithelial intercellular adhesion may influence disease severity. Disruption of adherens junction (AJ) protein E‐cadherin has a well‐established role in carcinogenesis. Calpain family proteases are upregulated in several types of adenocarcinoma and can cleave E‐cadherin to a functionally‐impaired 100kDa form. AIMS: 1) to determine the effects of Hp on calpains, 2) to assess the role of calpains in Hp‐induced AJ alterations. RESULTS: Epithelial (SCBN) monolayers challenged with Hp strain SS1 or 60190 for 24h had increased calpain activity and elevated levels of the cleaved form of the calpain substrate α‐spectrin, as determined by activity assay and immunoblotting. Immunoblotting for the μ and m calpain isoforms revealed that μ, but not m, calpain is activated in response to Hp. Immunostaining and western blotting of subcellular fractions revealed loss of membrane‐associated E‐cadherin and increased cytosolic E‐cadherin. Western blotting of whole cell lysates demonstrated that Hp challenge induced cleavage of the 120kDa full‐length E‐cadherin to a 100kDa form. Calpain inhibition prevented these junctional defects. CONCLUSION: Carcinogenic Hp induces isoform‐specific calpain activation which results in E‐cadherin truncation in non‐tumorigenic epithelial cells. This work is funded by CIHR.