and/or aims): This is a revised renewal application to study the effect of UV radiation on certain aspects of epidermal keratinocyte membrane messenger systems. The major focus of the study is based on the fact that solar ultraviolet radiation is a ubiquitous environmental agent known to produce numerous effects in human skin including inflammation, pigmentation, alteration of immune function and carcinogenesis. The mechanism by which solar radiation evokes most cutaneous photobiological responses remains poorly defined. Specifically, little attention has been paid to the possible role of membrane constituents in mediation of UV-induced skin changes. Based on epidemiological studies, it is known that UV-induced skin damage results in stimulation of many biologic processes analogous to changes induced by membrane active agents - hormones, growth factors and chemical tumor-promoters. These agents are known to act through alteration in membrane structure and function including phospholipase activation and membrane receptor/kinase activation, resulting in the activation of second messenger signals. In turn, these second messenger systems play a crucial role in regulation of cell growth and differentiation in both normal skin and in skin diseases such as psoriasis and cancer. The overall objective of the proposed studies is to examine the effect of UV radiation on selected aspects of membrane messenger system metabolism in human epidermis. The four specific aims are to utilize human keratinocytes in culture as a model to assay the effect of UV radiation (UVB-290-320 nm; UVA-302-400 nm) on phospholipase activation and diacylglycerol (DAG) production, protein kinase C (PKC) abundance and activity, alterations of binding of epidermal growth factor (EGF) to its receptor. Finally, the investigator will assay cellular proliferation by labelled thymidine incorporation and cell counting; and cellular differentiation by envelope counting. It is proposed that the delineation of the effect of UV on membrane messenger system metabolism of human keratinocytes should yield insight into the role played by such effects on the overall tissue response of human skin to sunlight, extending the knowledge of how UV radiation induces deleterious effects in normal skin and positive effect in diseased skin as occurs in phototherapy of psoriasis.
| Matsui, M S; DeLeo, V A (1990) Induction of protein kinase C activity by ultraviolet radiation. Carcinogenesis 11:229-34 |
