Abstract
Photodynamic therapy (PDT) based on photoproduction of highly toxic singlet oxygen, which causes oxidative stress and death of stained cells, is used for treatment of cancer including that of brain tumors. The study of signaling and epigenetic mechanisms of photodynamic damage of normal neurons and glial cells was carried out on isolated crayfish mechanoreceptors consisting of single sensory neurons enveloped by glial cells. PDT effect caused necrosis of neurons and glial cells and apoptosis of glial cells. Application of specific inhibitors or activators of transcription factors: NF-?B (betulinic acid, parthenolide, CAPE), AP-1 (SR11302), STAT-3 (cucurbitacin, stattic), HIF-1 (KG-548, FM19G11, DMOG), and p53 (RITA, WR1065, nutlin-3, pifithrin-a) or those of epigenetic processes, such as DNA methylation (5-azacytidine, decitabine) or histone deacetylation (sodium valproate, trichostatin A, SBHA) demonstrated that PDTinduced death of neurons and glial cells is regulated by transcription factors and epigenetic regulators. Epigenetic processes did not influence PDT-induced necrosis of neurons. Among the transcription factors studied, only STAT-3 was involved in PDT-induced necrosis of neurons. DNA methylation and histone deacetylation, which suppress transcription, mediated PDT-induced necrosis of glial cells. The transcription factor NF-?B had antinecrotic effects on glia. All transcription factors studied and histone deacetylase were involved in apoptosis of glial cells. Their modulators might serve as potential gliaand neuroprotective agents.
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Original Russian Text © A.B. Uzdensky, E.V. Berezhnaya, V.D. Kovaleva, M.A. Neginskaya, M.V. Rudkovskii, S.A. Sharifulina, 2015, published in Biologicheskie Membrany, 2015, Vol. 32, No. 5–6, pp. 437–445.
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Uzdensky, A.B., Berezhnaya, E.V., Kovaleva, V.D. et al. The response of neurons and glial cells of crayfish to photodynamic treatment: Transcription factors and epigenetic regulation. Biochem. Moscow Suppl. Ser. A 9, 329–336 (2015). https://doi.org/10.1134/S1990747815050190
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DOI: https://doi.org/10.1134/S1990747815050190