Sulfur mustard causes caspase-mediated cleavage of cytoskeletal keratins
conference paper
In order to study the toxic mechanism of action of sulfur mustard (HD), we examined protein expression in control and HD-treated cultured human epidermal keratinocytes (HEK) at 24 h after exposure to 100 μM HD. Protein patterns of cell lysates were prepared using two-dimensional gel electrophoresis with an immobilized pH gradient in the first dimension between 4 and 7 and a molecular weight range in the second dimension between 20 and 200 kDa. Most of the new spots that were observed in the protein profile of HD-exposed HEK, were identified as N- and C-terminal fragments of keratins 14, 16 and 17. These fragments are due to cleavage by caspases, which are proteases responsible for apoptosis, since inhibitors of caspase-3, caspase-6 or of all caspases can prevent the HD-induced keratin degradation. These results indicate that apoptosis is involved in HD-induced cytotoxicity of cultured HEK and that prevention of apoptosis is an option for therapeutic intervention.
TNO Identifier
526866
Source title
Bioscience 2004 "Medical Chemical Defense Research for the Warfighter and Homeland Defense", US Army Medical Defense Bioscience Review, 18-21 May 2004
Collation
9 p.
Pages
Chapter 221
Files
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