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Protection of the Crayfish Mechanoreceptor Neuron and Glial Cells from Photooxidative Injury by Modulators of Diverse Signal Transduction Pathways

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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.

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Acknowledgments

The work was supported by grants of the Russian Scientific Foundation (14-15-00068) and Russian Foundation for Basic Research (05-04-48440; 08-04-01322; 11-04-01476; 14-04-00741).

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachky Ave., Rostov-on-Don, 344090, Russia

    Anatoly Uzdensky, Elena Berezhnaya, Andrej Khaitin, Vera Kovaleva, Maxim Komandirov, Maria Neginskaya, Mikhail Rudkovskii & Svetlana Sharifulina

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  1. Anatoly Uzdensky
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  2. Elena Berezhnaya
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  3. Andrej Khaitin
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Uzdensky, A., Berezhnaya, E., Khaitin, A. et al. Protection of the Crayfish Mechanoreceptor Neuron and Glial Cells from Photooxidative Injury by Modulators of Diverse Signal Transduction Pathways. Mol Neurobiol 52, 811–825 (2015). https://doi.org/10.1007/s12035-015-9237-8

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