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NSAIDs Inhibit Activity and Reduce Surface Expression of Calpain Proteases
Author(s) -
Silver Kristopher,
LeLoup Ludovic,
Freeman Lisa C,
Wells Alan,
Lillich James D
Publication year - 2010
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.24.1_supplement.583.2
Subject(s) - calpain , proteases , microbiology and biotechnology , cell , chemistry , cell migration , cysteine protease , biology , biochemistry , enzyme
Non‐steroidal anti‐inflammatory drugs (NSAIDs) are among the most commonly used drugs worldwide; however, chronic treatment with NSAIDs can result in gastrointestinal toxicity (GI). Previously, we have reported that NSAIDs associated with GI damage inhibit migration of cultured epithelial cells and suppress the expression of calpains, a family of cysteine proteases important in many cellular processes including cell migration. Accordingly, we examined calpain activity in monolayers of intestinal epithelial cells treated with NSAIDs using a calpain‐selective fluorescent reporter in living cells (t‐BOC). Additionally, we used a cell membrane footprinting technique to examine expression of calpains at the cell membrane attached to the substrate. Our results demonstrate that NSAIDs with ulcerogenic potential depress calpain activity within 24 h of treatment. Furthermore, NSAID treatment also inhibited localization of calpain proteases to the basal cell membrane and disrupted the formation of actin filaments. Thus, inhibition of epithelial cell migration by NSAIDs may result from disruption of calpain signaling and altered cytoskeletal organization. As these represent activities that are in addition to and not responsible for the immunosuppressive actvity, these findings open avenues for adjuvant treatments to minimize these morbid and even mortal consequences of these toxicities.