Implications of Protein Alkyation and Proteolysis on Vesication Caused by Sulfur Mustard
Abstract
In this report the results are described of studies on protein alkylation and on proteolytic activity in human skin ex vivo or in cultured human keratinocytes after exposure to sulfur mustard (HD). Hypothetically, these two events can lead to the destruction of the epidermal-dermal junction of the skin after exposure to HD. On microgram basis, proteins in the skin become alkylated by HD to the same extent as DNA or RNA and in proportion to the amount of HD used. Keratins, that are the most abundantly present proteins in epidermis, bind half of the available HD. In addition, two- dimensional gel electrophoresis shows that HD binds with preference to a selection of the proteins of the non-keratin protein pool. The observed alkylation of keratin and selected proteins may have consequences for the functioning of basal cells. Matrix metalloproteases (MMPs) play a role in the weakening of cutaneous basement membrane zone following HE) exposure. In the presence of specific inhibitors of MMPs, BB94 or BB3103, no epidermal-dermal separation occurred in human skin ex vivo. However, neither upregulated expression of MMPs, nor reduced expression of tissue inhibitors of metalloproteinases (TIMPs) are responsible for HD-induced epidermal-dermal separation. The results suggest that HE) causes a disturbance of the basement membrane protein homeostasis as a result of diminished availability or binding capacity of the adhesion molecules rather than of enhanced degradation. Therapeutic treatment of HD-exposed skin with MMP inhibitors will keep epidermis and dermis together, thereby eliminating one of the causal factors of vesication.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADB257215
Entities
People
- Marike A. Mol
Organizations
- Prins Maurits Laboratorium TNO