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The Localization of p53 in the Crayfish Mechanoreceptor Neurons and Its Role in Axotomy-Induced Death of Satellite Glial Cells Remote from the Axon Transection Site

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Abstract

Neuron and glia death after axon transection is regulated by various signaling proteins. Protein p53 is a key regulator of diverse cell functions including stress response, DNA repair, proliferation, and apoptosis. We showed that p53 was overexpressed in crayfish ganglia after bilateral axotomy. In the isolated crayfish stretch receptor, a simple natural neuroglial preparation, which consists of a single mechanoreceptor neuron (MRN) enveloped by glial cells, p53 regulated axotomy-induced death of glial cells remote from the axon transection site. In MRN, p53 immunofluorescence was highest in the nucleolus and in the narrow cytoplasmic ring around the nucleus; its levels in the nucleus and cytoplasm were lower. After axotomy, p53 accumulated in the neuronal perikaryon. Its immunofluorescence also increased in the neuronal and glial nuclei. However, p53 immunofluorescence in the most of neuronal nucleoli disappeared. Axotomy-induced apoptosis of remote glial cells increased in the presence of p53 activators WR-1065 and nutlin-3 but reduced by pifithrin-α that inhibits transcriptional activity of p53. Pifithrin-μ that inhibits p53 effect on mitochondria increased axotomy-induced apoptosis of remote glial cells but reduced their necrosis. Therefore, axotomy-induced apoptosis of remote glial cells was associated with p53 effect on transcription processes, whereas glial necrosis was rather associated with transcription-independent p53 effect on mitochondria. Apparently, the fate of remote glial cells in the axotomized crayfish stretch receptor is determined by the balance between different modalities of p53 activity.

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Funding

The work was supported by the Ministry of Education and Science of Russian Federation, grants #6.6324.2017/8.9 and 6.4951.2017/6.7.

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Stanislav Rodkin: Immunofluorescence study of p53 localization in neuron and glial cells

Andrey Khaitin: Immunofluorescence study of p53 localization in neuron and glial cells and study of effects of pifithrin-α and pifithrin-μ on neurons and glial cells

Maria Pitinova: Study of effects of pifithrin-α and pifithrin-μ on neurons and glial cells

Valentina Dzreyan: Immunoblotting of p53 expression in VNC ganglia

Valeria Guzenko: Immunoblotting of p53 expression in VNC ganglia

Mikhail Rudkovskii: Study of effects of RITA on neurons and glial cells

Svetlana Sharifulina: Study of effects of nutlin-3 and WR-1065 on neurons and glial cells

Anatoly Uzdensky: Work management; analysis of results, and writing the paper

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Correspondence to Anatoly Uzdensky.

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Rodkin, S., Khaitin, A., Pitinova, M. et al. The Localization of p53 in the Crayfish Mechanoreceptor Neurons and Its Role in Axotomy-Induced Death of Satellite Glial Cells Remote from the Axon Transection Site. J Mol Neurosci 70, 532–541 (2020). https://doi.org/10.1007/s12031-019-01453-2

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  • DOI: https://doi.org/10.1007/s12031-019-01453-2

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