|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1995 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1994 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1993 : ¥900,000 (Direct Cost : ¥900,000)
There are various bioactive radicals and arachidonate (AA) metabolites involved in UV-induced damage. Of linoliate (LA) metabolites similar in chemical structure, leukotoxin (LX) is regarded as an aggravating aget, while 13 HODE (13-hydroxyoctadecadienoic acid, 13-hydroxylinoleic acid) is regarded as a beneficial agent with radical scavenging or anti-inflammatory effects. The pathway producing LX and the enzyme producing 13HODE in the skin have not been clarified yet. The metabolism of LA in the skin, which seems to be physiologically and clinically important, is uncertain, either.
We studied the metabolism of LA in the skin and the effect of UV exposure on it. Epidermal homogenates of hairless mice produced material with 234 nm UV absorption different from AA metabolites, which was identified as a mixture of 13HODE and 9HODE.Enzymatic properties for the production of these HODEs in the skin homogenate are almost identical with those of cyclooxygenase (COX). Immunological approach to re
veal the identity of 1%-Tween 20-solubilized enzyme with conventional COX 1 has not been successful yet. After UV exposure, 13HODE gradually increased, reached the maximum in 2hs and returned to the normal level in 24 hs. Application of GC/MS and HPLC was tried to measure LX.HPLC was adopted because of its additional capability of detecting LA in the same method. In UV-unexposed skin, LX-like material was not present, whereas a trace amount of LA was detected. After UV exposure, very small amounts of LX appeared and substantial amounts of LA was produced, gradually increased to reach a maximum in approx. 2-3 hs and returned to the normal level in 24 hs. These results suggest that 13HODE is possibly produced by a certain COX and activations of PLA2 have something to do with production of 13HODE and LX-like material. Induction of the enzymes producing 13HODE or Lx has not been clarified yet. There remains a possibility that these two materials were released from esterified lipids by activation of PLA2. Further study is needed along this line. Less