STIMULATION OF STRESS-ACTIVATED PROTEIN-KINASE AND P38 HOG1 KINASE INMURINE KERATINOCYTES FOLLOWING PHOTODYNAMIC THERAPY WITH BENZOPORPHYRIN DERIVATIVE

The activation state of the members of the mitogen-activated protein k inase family following photodynamic therapy (PDT) with benzoporphyrin derivative monoacid ring A was investigated using a naturally transfor med murine keratinocyte cell line, Pam 212. PDT involves the use of ph otosensitizer molecules and a specific wavelength of visible light. Th e process of PDT generates singlet oxygen and other reactive oxygen in termediates (ROIs), and the cytotoxic effect of these ROIs is the basi s for the use of PDT to treat cancer and psoriasis. PDT caused a stron g dose- and time-dependent activation of both stress-activated protein kinase (SAPK) and p38 HOG1. The maximum activation of SAPK and p38 HO G1 occurred between 20 and 30 min following PDT treatment with 200 ng/ ml benzoporphyrin derivative monoacid ring A and 2 J/cm(2) of red ligh t at 690 nm. In our system, PDT did not cause significant activation o f extracellularly regulated kinase (ERK) 1 and ERK2. Under the same ex perimental conditions, ultraviolet light irradiation caused strong act ivation of SAPK and p38 HOG1 and minimum activation of ERK1 and ERK2 i n Pam212 cells. A number of ROI scavengers were tested for their effec t on PDT-induced SAPK and p38 HOG1 activation. Both L-histidine and N- acetyl-L-cysteine showed a significant inhibitory effect on PDT-induce d SAPK and p38 HOG1 activation. This indicated that PDT-induced SAPK a nd p38 HOG1 activation may be partially mediated by ROI.