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Apoptosis due to sulfur mustard (SM) in human epidermal keratinocytes (NHEK) and human airway epithelial cells (HAEC): Mechanisms and intervention
SM (bis‐(2‐chloroethyl) sulfide), commonly called mustard gas, is a chemical warfare compound and a potential terrorism agent. SM exposure causes debilitating skin blisters and injuries to the eyes and the respiratory system. One of the mechanisms of SM toxicity is via epithelial damage in the affec...
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Published in: | The FASEB journal 2006-03, Vol.20 (4), p.A121-A121 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | SM (bis‐(2‐chloroethyl) sulfide), commonly called mustard gas, is a chemical warfare compound and a potential terrorism agent. SM exposure causes debilitating skin blisters and injuries to the eyes and the respiratory system. One of the mechanisms of SM toxicity is via epithelial damage in the affected tissues, particularly basal cell apoptosis, which may occur via multiple pathways involving (a) abnormal Ca2+/calmodulin (CaM)‐dependent mechanisms, (b) disturbed cellular bioenergetics, and (c) Fas (death receptor)/Fas ligand (FasL) interactions. We characterized the apoptosis pathways by studying pathway‐specific caspases, the cysteine protease group of enzymes activated in apoptosis. We determined caspase activity by assay of fluorogenic caspase type‐specific peptide substrate hydrolysis. We studied caspase processing, i.e., proteolytic conversion of procaspase to active caspase by immunoblot analyses utilizing caspase type‐specific antibodies. Results in both NHEK and HAEC indicated that SM activates (a) caspase‐9, an indicator of the Ca2+/CaM‐mediated mitochondrial pathway, (b) caspase‐8, a marker for the Fas‐mediated pathway, and (c) caspase‐3/7, the executioner caspase involved in both pathways. Peptide caspase inhibitors specific for either caspase‐3/7 (AC‐DEVD‐CHO) or caspase‐8 (AC‐IETD‐CHO) added to cells prior to SM decreased apoptosis. These observations suggest apoptosis as a mechanism of SM toxicity and caspase inhibitors as prospective medical countermeasures. |
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ISSN: | 0892-6638 1530-6860 |
DOI: | 10.1096/fasebj.20.4.A121 |