Photodynamic inactivation of isolated crayfish neuron requires protein kinase C, PI 3-kinase and Ca2+.
Involvement of some signalling pathways in response to photodynamic therapy (PDT) of sulfonated aluminium phthalocyanine Photosens has been studied in isolated nerve cell. Neurone photosensitisation with 10(-7) M Photosens gradually inhibited firing and irreversibly abolished neuronal activity. Activation of protein kinase C (PKC) by phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) precipitated PDT-induced abolition of neurone activity and caused nucleus swelling and impairment of the nucleus border. Elevation of cytosolic Ca(2+) concentration by ionomycin or thapsigargin also reduced neurone lifetime. In contrast, the PKC inhibitors staurosporine, hypericin or chelerythrine as well as the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitors wortmannin or LY294002 increased neurone lifetime. These results showed that PKC, PI 3-kinase and Ca(2+) are involved in PDT-induced neurone inactivation and following death.
Bragin
Denis E
DE
Department of Biophysics, Institute for Neurocybernetics, Rostov State University, 194/1 Stachky ave., Rostov-on-Don, 344090, Russia.
Kolosov
Mikhail S
MS
Uzdensky
Anatoly B
AB
D000818:Animals; D003400:Astacoidea; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010778:Photochemotherapy; D011493:Protein Kinase C / Q000378:metabolism*
D007211:Indoles; D009942:Organometallic Compounds; C060570:aluminum phthalocyanine; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D002118:Calcium