The flashlights on a distinct role of protein kinase C δ: Phosphorylation of regulatory and catalytic domain upon oxidative stress in glioma cells

• Published in: Cellular signalling 2017-06, Vol.34, p.11-22
• Main Authors: Misuth, Matus, Joniova, Jaroslava, Horvath, Denis, Dzurova, Lenka, Nichtova, Zuzana, Novotova, Marta, Miskovsky, Pavol, Stroffekova, Katarina, Huntosova, Veronika
• Format: Article
• Language: English
• Subjects: Algorithms; Apoptosis - drug effects; Apoptosis - radiation effects; Bcl-2; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Catalytic Domain; Cell Line, Tumor; Glioma - metabolism; Glioma - pathology; Golgi apparatus; Heterogeneity; Humans; Hypericin; Light; Microscopy, Electron; Microscopy, Fluorescence; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Oxidative Stress - drug effects; Oxidative Stress - radiation effects; Perylene - analogs & derivatives; Perylene - pharmacology; Phosphorylation - drug effects; Phosphorylation - radiation effects; Photodynamic therapy; Protein kinase C; Protein Kinase C-delta - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Serine 645; Statistical morphology; Tyrosine 155
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2017.02.020

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. [Display omitted] •Golgi apparatus may be a source of light-induced reactive oxygen species (ROS) in glioma cells•light induced ROS revealed PKCδ phosphorylation at the Ser645 site in the cytoplasm and at the Tyr155 site in nucleus•the phosphorylation of the PKCδ catalytic domain may be involved in phosphorylation of Bcl-2 in the nucleus•the phosphorylation of the PKCδ regulatory domain may participate in Bcl-2 phosphorylation in cytoplasm and mitochondria•PKCδ localized in Golgi apparatus, and endoplasmic related areas may regulate the balance between cell recovery and demise