title: Protection of the Crayfish Mechanoreceptor Neuron and Glial Cells from Photooxidative Injury by Modulators of Diverse Signal Transduction Pathways.
abstract: Oxidative stress is the reason of diverse neuropathological processes. Photodynamic therapy (PDT), an effective inducer of oxidative stress, is used for cancer treatment, including brain tumors. We studied the role of various signaling pathways in photodynamic injury and protection of single neurons and satellite glial cells in the isolated crayfish mechanoreceptor. It was photosensitized with alumophthalocyanine Photosens in the presence of inhibitors or activators of various signaling proteins. PDT eliminated neuronal activity and killed neurons and glial cells. Inhibitory analysis showed the involvement of protein kinases Akt, glycogen synthase kinase-3β (GSK-3β), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinases 1 and 2 (MEK1/2), calmodulin, calmodulin-dependent kinase II (CaMKII), adenylate cyclase, and nuclear factor NF-κB in PDT-induced necrosis of neurons. Nitric oxide (NO) and glial cell-derived neurotrophic factor (GDNF) reduced neuronal necrosis. In glial cells, protein kinases Akt, calmodulin, and CaMKII; protein kinases C and G, adenylate cyclase, and p38; and nuclear transcription factor NF-κB also mediated PDT-induced necrosis. In contrast, NO and neurotrophic factors nerve growth factor (NGF) and GDNF demonstrated anti-necrotic activity. Phospholipase Cγ, protein kinase C, GSK-3β, mTOR, NF-κB, mitochondrial permeability transition pores, and NO synthase mediated PDT-induced apoptosis of glial cells, whereas protein kinase A, tyrosine phosphatases, and neurotrophic factors NGF, GDNF, and neurturin were involved in protecting glial cells from photoinduced apoptosis. Signaling pathways that control cell survival and death differed in neurons and glia. Inhibitors or activators of some signaling pathways may be used as potential protectors of neurons and glia from photooxidative stress and following death.
authors.affiliation: Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachky Ave., Rostov-on-Don, 344090, Russia, auzd@yandex.ru.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Uzdensky
authors.forename: Elena
authors.initials: E
authors.lastname: Berezhnaya
authors.forename: Andrej
authors.initials: A
authors.lastname: Khaitin
authors.forename: Vera
authors.initials: V
authors.lastname: Kovaleva
authors.forename: Maxim
authors.initials: M
authors.lastname: Komandirov
authors.forename: Maria
authors.initials: M
authors.lastname: Neginskaya
authors.forename: Mikhail
authors.initials: M
authors.lastname: Rudkovskii
authors.forename: Svetlana
authors.initials: S
authors.lastname: Sharifulina
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D003400:Astacoidea / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008027:Light / Q000009:adverse effects*; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D016328:NF-kappa B / Q000502:physiology; D009336:Necrosis; D009414:Nerve Growth Factors / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009569:Nitric Oxide / Q000502:physiology; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects*; D051966:Phospholipase C gamma / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D010778:Photochemotherapy / Q000009:adverse effects*; D011494:Protein Kinases / Q000502:physiology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D016328:NF-kappa B; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C048577:aluminum tetrasulfophthalocyanine; D009569:Nitric Oxide; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D051966:Phospholipase C gamma