title: The flashlights on a distinct role of protein kinase C δ: Phosphorylation of regulatory and catalytic domain upon oxidative stress in glioma cells.
abstract: Glioblastoma multiforme are considered to be aggressive high-grade tumors with poor prognosis for patient survival. Photodynamic therapy is one of the adjuvant therapies which has been used for glioblastoma multiforme during last decade. Hypericin, a photosensitizer, can be employed in this treatment. We have studied the effect of hypericin on PKCδ phosphorylation in U87 MG cells before and after light application. Hypericin increased PKCδ phosphorylation at tyrosine 155 in the regulatory domain and serine 645 in the catalytic domain. However, use of the light resulted in apoptosis, decreased phosphorylation of tyrosine 155 and enhanced serine 645. The PKCδ localization and phosphorylation of regulatory and catalytic domains were shown to play a distinct role in the anti-apoptotic response of glioma cells. We hypothesized that PKCδ phosphorylated at the regulatory domain is primarily present in the cytoplasm and in mitochondria before irradiation, and it may participate in Bcl-2 phosphorylation. After hypericin and light application, PKCδ phosphorylated at a regulatory domain which is in the nucleus. In contrast, PKCδ phosphorylated at the catalytic domain may be mostly active in the nucleus before irradiation, but active in the cytoplasm after the irradiation. In summary, light-induced oxidative stress significantly regulates PKCδ pro-survival and pro-apoptotic activity in glioma cells by its phosphorylation at serine 645 and tyrosine 155.
authors.affiliation: Department of Biophysics, Faculty of Sciences, P. J. Safarik University in Kosice, Jesenna 5, 041 54, Kosice, Slovakia.
authors.forename: Matus
authors.initials: M
authors.lastname: Misuth
authors.affiliation: Department of Biophysics, Faculty of Sciences, P. J. Safarik University in Kosice, Jesenna 5, 041 54, Kosice, Slovakia.
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Joniova
authors.affiliation: Center for Interdisciplinary Biosciences, Faculty of Sciences, P.J. Safarik University in Kosice, Jesenna 5, 041 54, Kosice, Slovakia.
authors.forename: Denis
authors.initials: D
authors.lastname: Horvath
authors.affiliation: Department of Biophysics, Faculty of Sciences, P. J. Safarik University in Kosice, Jesenna 5, 041 54, Kosice, Slovakia.
authors.forename: Lenka
authors.initials: L
authors.lastname: Dzurova
authors.affiliation: Department of Muscle Cell Research, Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Science, Bratislava, Slovakia.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Nichtova
authors.affiliation: Department of Muscle Cell Research, Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Science, Bratislava, Slovakia.
authors.forename: Marta
authors.initials: M
authors.lastname: Novotova
authors.affiliation: Center for Interdisciplinary Biosciences, Faculty of Sciences, P.J. Safarik University in Kosice, Jesenna 5, 041 54, Kosice, Slovakia; SAFTRA Photonics Ltd., Jesenna 5, 041 54, Kosice, Slovakia.
authors.forename: Pavol
authors.initials: P
authors.lastname: Miskovsky
authors.affiliation: Department of Biophysics, Faculty of Sciences, P. J. Safarik University in Kosice, Jesenna 5, 041 54, Kosice, Slovakia; Center for Interdisciplinary Biosciences, Faculty of Sciences, P.J. Safarik University in Kosice, Jesenna 5, 041 54, Kosice, Slovakia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Stroffekova
authors.affiliation: Center for Interdisciplinary Biosciences, Faculty of Sciences, P.J. Safarik University in Kosice, Jesenna 5, 041 54, Kosice, Slovakia. Electronic address: veronika.huntosova@upjs.sk.
authors.forename: Veronika
authors.initials: V
authors.lastname: Huntosova
mesh_terms: D000465:Algorithms; D000873:Anthracenes; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008027:Light; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects*; D010569:Perylene / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D051745:Protein Kinase C-delta / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: D000873:Anthracenes; D019253:Proto-Oncogene Proteins c-bcl-2; D010569:Perylene; C004965:hypericin; D051745:Protein Kinase C-delta
keywords: Bcl-2; Golgi apparatus; Heterogeneity; Hypericin; Mitochondria; Photodynamic therapy; Protein kinase C; Serine 645; Statistical morphology; Tyrosine 155