title: On the role of phosphatidylinositol 3-kinase, protein kinase b/Akt, and glycogen synthase kinase-3β in photodynamic injury of crayfish neurons and glial cells.
abstract: Photodynamic treatment that causes intense oxidative stress and cell death is currently used in neurooncology. However, along with tumor cells, it may damage healthy neurons and glia. To study the involvement of signaling processes in photodynamic injury or protection of neurons and glia, we used crayfish mechanoreceptor consisting of a single neuron surrounded by glial cells. It was photosensitized with alumophthalocyanine Photosens. Application of specific inhibitors showed that phosphatidylinositol 3-kinase did not participate in photoinduced death of neurons and glia. Akt was involved in photoinduced necrosis but not in apoptosis of neurons and glia. Glycogen synthase kinase-3β participated in photoinduced apoptosis of glial cells and in necrosis of neurons. Therefore, phosphatidylinositol 3-kinase/protein kinase Akt/glycogen synthase kinase-3β pathway was not involved as a whole in photodynamic injury of crayfish neurons and glia but its components, Akt and glycogen synthase kinase-3β, independently and cell specifically regulated death of neurons and glial cells. According to these data, necrosis in this system was a controlled but not a non-regulated cell death mode. The obtained results may be used for the search of pharmacological agents selectively modulating death and survival of normal neurons and glial cells during photodynamic therapy of brain tumors.
authors.affiliation: Department of Biophysics and Biocybernetics, Institute of Neurocybernetics, Southern Federal University, 194/1 Stachky Ave., NII NK, Rostov-on-Don 344090, Russia.
authors.forename: Maxim A
authors.initials: MA
authors.lastname: Komandirov
authors.forename: Evgeniya A
authors.initials: EA
authors.lastname: Knyazeva
authors.forename: Yulia P
authors.initials: YP
authors.lastname: Fedorenko
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Rudkovskii
authors.forename: Denis A
authors.initials: DA
authors.lastname: Stetsurin
authors.forename: Anatoly B
authors.initials: AB
authors.lastname: Uzdensky
mesh_terms: D000818:Animals; D003400:Astacoidea / Q000166:cytology / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007211:Indoles / Q000494:pharmacology; D008027:Light / Q000009:adverse effects; D008465:Mechanoreceptors / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D009942:Organometallic Compounds / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010778:Photochemotherapy / Q000009:adverse effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D009942:Organometallic Compounds; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011838:Radiation-Sensitizing Agents; C048577:aluminum tetrasulfophthalocyanine; D058539:Phosphatidylinositol 3-Kinase; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3