ACTIVATION OF JNK AND P38 BUT NOT ERK MAP KINASES IN HUMAN SKIN CELLSBY 5-AMINOLEVULINATE-PHOTODYNAMIC THERAPY

5-Aminolevulinate (ALA) photodynamic therapy (PDT) is being used clini cally for the treatment of skin cancers. ALA is applied as a precursor of porphyrins serving as endogenous photosensitizers. Irradiation of Ha-CaT cells preincubated with 1 mM ALA for 24 h with red light of 570 -750 nm at a dose of 4.5 J/cm(2) Leads to a 6-fold elevation of cellul ar c-Jun N-terminal kinase activity; phosphorylation of p38 mitogen-ac tivated protein kinase (MAPK) is enhanced to a similar extent. In cont rast, neither activation nor increased phosphorylation of the extracel lular stimulus-regulated kinase MAPKs is detected. p38 is also phospho rylated by ALA-PDT in the human melanoma cell lines Bro and SkMel-23, applying doses that lead to 80-95% cell death after 24 h, Hence, the e ffects of ALA-PDT on MAPKs are similar to stresses like UV irradiation or exposure to hydrogen peroxide with respect to activation of JNK an d p38 MAPKs, They are different, however, in that extracellular stimul us-regulated kinase activity is not raised by ALA-PDT.