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Human bronchial/tracheal epithelial cells (BEC) are more sensitive than small airway epithelial cells (SAEC) to sulfur mustard‐induced apoptosis apparently due to a Fas (death receptor) response amplification loop
Author(s) -
Ray R.,
Keyser B.,
Andres D.,
Hauck S.,
Benton B.,
Carpin C.,
Daher A.,
SimbulanRosenthal C.,
Rosenthal D.
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.648.6
Subject(s) - caspase , apoptosis , sulfur mustard , microbiology and biotechnology , chemistry , caspase 8 , caspase 3 , cancer research , programmed cell death , biology , biochemistry , toxicity , organic chemistry
Sulfur mustard (SM; bis‐(2‐chloroethyl) sulfide) causes skin blisters, airway injury and ocular damage. Apoptosis is one of its mechanisms of action. Here, we examined SM‐induced apoptosis pathways in vitro in cultured BEC and SAEC. At 16 h after cells were exposed to increasing SM concentrations (0, 50, 100, 300μM), apoptosis pathways were characterized by (a) measuring hydrolysis of fluorogenic substrates of caspases‐3, ‐8 and ‐9, and (b) studying the effects of caspase type‐specific peptide inhibitors on each caspase activity. SM activated caspase‐8 and caspase‐3 in both cell types, but caspase‐9 only in BEC. Immunoblot analyses revealed proteolytic processing of the proenzymes to the active forms of caspases‐8 and ‐3. Moreover, caspases were activated at a lower SM concentration in BEC than in SAEC. Each caspase type‐specific inhibitor tested was most effective for that particular caspase, but also inhibited other caspases. These results lead to the following conclusions. BEC are more sensitive to SM‐induced apoptosis than SAEC. This is due to a mechanism of Fas response (caspase‐8 activation) stimulation via an amplification loop involving caspases‐8, ‐9, ‐3 and ‐6 in BEC, but not in SAEC. These findings may be useful in developing therapeutics against SM injury. Research supported by JSTO‐CBD Award # M0005_04_RC_C. The views represented are those of the authors and are not necessarily endorsed by the US Army.