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Giardia duodenalis cysteine cathepsin proteases and their role in intestinal disease
Author(s) -
Bhargava Amol,
Cotton James A.,
Yates Robin,
Buret Andre G.
Publication year - 2013
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.27.1_supplement.647.7
Subject(s) - giardia , proteases , cathepsin , cathepsin l , microbiology and biotechnology , biology , cathepsin b , cysteine protease , mucus , secretion , biochemistry , enzyme , ecology
Giardia duodenalis , an enteric protozoan parasite, induces pathophysiological effects shared with chronic gastrointestinal disorders, including barrier function disruption, via unknown mechanisms. Cysteine proteases, also identified in the Giardia genome, are implicated in disease pathophysiology of other protozoan parasites. Objective To characterize and determine a role for cysteine cathepsins in the pathogenesis of giardiasis. Results In vitro cathepsin B/L activity was detected within Giardia trophozoites and in co‐culture supernatants. Giardia trophozoites increased cathepsin B activity in host enterocytes during co‐cultures; this required trophozoite adhesion to host cells. Pretreating Giardia trophozoites with Ca‐074Me (a cathepsin B specific inhibitor) prevented elevation of cathepsin activity in host cells. Inhibition of Giardia cathepsins with a cysteine protease inhibitor (E64) prevented the alteration of the mucus layer glycoprotein, MUC‐2; however, Ca‐074Me failed to prevent Giardia ‐induced ZO‐1 cleavage. Conclusion Giardia trophozoites increase cathepsin activity in host cells and express cathepsins that play a role in mucus alteration. Supported by NSERC, AIHS, CCFC.