John Reilly's Homepage Dr. John Reilly Department of Chemistry and Physics Coastal Carolina University SCI 216-D (843) 349-6468 jreilly@coastal.edu

Research Inhibition of Histidase Via PUVA Therapy Psoralen-UVA (PUVA) is an important therapeutic tool in treating dermatological ailments such as psoriasis. However, we are far from completely understanding the mechanisms, and adverse effects, underlying photochemotherapy. There is strong evidence to suggest that PUVA treatment affects the immune system. It is known to affect antigen-presenting cells, damage DNA, and increase the risk of squamous cell carcinoma. Additionally, PUVA reacts with proteins, RNA, lipids and also affects enzyme activity. Trans-Urocanic acid, which is produced by histidase in skin, has been considered a natural sunscreen because its UV absorption spectrum overlaps with that of DNA. Presently it is considered a photoreceptor for immuno-suppression. Trans-UCA undergoes isomerization to cis-UCA when exposed to UVB light. Cis-UCA has been implicated in immuno-suppression. If PUVA therapy inhibits the production of trans-UCA in the skin by inhibiting histidase, then this may suggest that PUVA therapy increases the skin’s susceptibility to photo-damage and mutagenesis. However, if less t-UCA is produced then, in turn, less c-UCA will be produced. How does the suppression of t-UCA, acting as a natural photoreceptor, and c-UCA, acting as a photo-immunosuppressant, affect the overall immunosuppression of patients undergoing PUVA therapy? Using an enzymatic assay we monitor the growth of the t-UCA peak at 277 nm to determine the effect of PUVA therapy has on the enzymatic catalysis of histidine to trans-urocanic acid. This research is an in vitro study that will be expanded to an in vivo study involving human subjects undergoing photochemotherapy to answer such questions as above. Cytochrome CYP3A4 and CYP3A5 Inhibition by 8-methoxypsoralen 15 years ago, an observation was made concerning the administering of a high blood-pressure drug, felodipine, with grapefruit juice.  Felodipine, when taken with grapefruit juice increased the plasma levels of felodipine in patients, lowering the patients blood pressure more than expected.  This suggested that something in the grapefruit juice was inhibiting the metabolic breakdown of the drug in the small intestine. In 2006, researchers were able to show that the cause of the increase in plasma levels was due to the inhibition of an important enzyme, known as cytochrome P450, found in the small intestine.  The cause of the inhibition was from a natural compound known as psoralen. The exact nature and mechanism of the inhibition was not investigated. This research is an in vitro study to determine the type, or mechanism, of enzyme inhibition. Organizations I belong to: American Chemical Society National Psoriasis Foundation Inter-American Photochemical Society International Union of Lure and Applied Chemists South Carolina Academy of Science Upcoming conferences: Big SURS (Southeast Undergraduate Research Symposium) to be held March 27-28th 2009. three of my students are presenting. Students are in bold Robert J. Kimble, Andrew J. O’Brien, Robert F. Holly and John T. Reilly.  Department of Chemistry and Physics, Coastal Carolina University, P.O. Box 261954 Conway, SC 29528.  Title: Cytochrome CYP3A4 and CYP3A5 inhibition by 8-methoxypsoralen Tiffiany R. Risher, Dominick A. Vitale, Trista Tyner, Kyle Troester and John T. Reilly.  Department of Chemistry and Physics, Coastal Carolina University, P.O. Box 261954 Conway, SC 29528.  Title: Photochemical inhibition of the enzyme histidase by PUVA therapy

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