Implications of Protein Alkylation and Proteolysis on Vesication Caused by Sulfur Mustard.
Abstract
Hypothetically, two possible causes underly the destruction of the epidermal-dermal junction of the skin after exposure to sulfur mustard (HD): improper functioning after HD-alkylation of proteins involved in the attachment structure, and breakdown of structural proteins by proteases. It will be of value to determine which of these processes occurs, in order to decide on the therapeutic strategy to be followed after exposure of skin to HD. In this report we describe the results so far of studies on protein alkylation and on proteolytic activity in skin or cultured keratinocytes after exposure to HD. After exposure of cultured human keratinocytes to C-14 HD, circa 40% of label present in cell lysates is bound to proteins. Alkylation preference is observed for K14, an acidic type I keratin. Some other proteins, with molecular weights of 100 - 200 kD and 30 - 40 kDa are also preferentially alkylated. Almost S5% of the label in cell lysates is bound to components other than DNA, RNA and protein, or not bound at all. The experiments on proteolytic activity demonstrate that there appears to be no role for matrix metalloproteinase (MMP)-9 in loosening the epidermal-dermal junction during RD-induced blistering. For MMP-2, it is doubtful whether its proteolytic activity is actually enhanced in HD-exposed skin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA377132
Entities
People
- Marijke A. Mol
Organizations
- Prins Maurits Laboratorium TNO