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Restoration of DNA Integrity and Cell Cycle by Electric Stimulation in Planarian Tissues Damaged by Ionizing Radiation

Devon Davidian, Melanie LeGro, Paul G. Barghouth, Salvador Rojas, Benjamin Ziman, Eli Isael Maciel, View ORCID ProfileDavid Ardell, Ariel L. Escobar, View ORCID ProfileNéstor J. Oviedo
doi: https://doi.org/10.1101/2021.05.16.444365
Devon Davidian
1Department of Molecular & Cell Biology, University of California, Merced, USA.
2Quantitative and Systems Biology Graduate Program, University of California, Merced, USA.
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Melanie LeGro
1Department of Molecular & Cell Biology, University of California, Merced, USA.
2Quantitative and Systems Biology Graduate Program, University of California, Merced, USA.
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Paul G. Barghouth
1Department of Molecular & Cell Biology, University of California, Merced, USA.
2Quantitative and Systems Biology Graduate Program, University of California, Merced, USA.
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Salvador Rojas
1Department of Molecular & Cell Biology, University of California, Merced, USA.
2Quantitative and Systems Biology Graduate Program, University of California, Merced, USA.
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Benjamin Ziman
1Department of Molecular & Cell Biology, University of California, Merced, USA.
2Quantitative and Systems Biology Graduate Program, University of California, Merced, USA.
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Eli Isael Maciel
1Department of Molecular & Cell Biology, University of California, Merced, USA.
2Quantitative and Systems Biology Graduate Program, University of California, Merced, USA.
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David Ardell
1Department of Molecular & Cell Biology, University of California, Merced, USA.
4Health Sciences Research Institute, University of California, Merced, USA.
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  • ORCID record for David Ardell
Ariel L. Escobar
3Department of Bioengineering, University of California, Merced, USA.
4Health Sciences Research Institute, University of California, Merced, USA.
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Néstor J. Oviedo
1Department of Molecular & Cell Biology, University of California, Merced, USA.
4Health Sciences Research Institute, University of California, Merced, USA.
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  • ORCID record for Néstor J. Oviedo
  • For correspondence: noviedo2@ucmerced.edu
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Abstract

Exposure to high levels of ionizing γ-radiation leads to irreversible DNA damage and cell death. Here, we establish that exogenous application of electric stimulation enables cellular plasticity to reestablish stem cell activity in tissues damaged by ionizing radiation. We show that sub-threshold direct current stimulation (DCS) rapidly restores pluripotent stem cell populations previously eliminated by lethally γ-irradiated tissues of the planarian flatworm Schmidtea mediterranea. Our findings reveal that DCS enhances DNA repair, transcriptional activity, and cell cycle entry in post-mitotic cells. These responses involve rapid increases in cytosolic [Ca2+] through the activation of L-type Cav channels and intracellular Ca2+ stores leading to the activation of immediate early genes and ectopic expression of stem cell markers in postmitotic cells. Overall, we show the potential of electric current stimulation to reverse damaging effects of high dose γ-radiation in adult tissues. Furthermore, our results provide mechanistic insights describing how electric stimulation effectively translates into molecular responses capable of regulating fundamental cellular functions without the need for genetic or pharmacological intervention.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 17, 2021.
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Restoration of DNA Integrity and Cell Cycle by Electric Stimulation in Planarian Tissues Damaged by Ionizing Radiation
Devon Davidian, Melanie LeGro, Paul G. Barghouth, Salvador Rojas, Benjamin Ziman, Eli Isael Maciel, David Ardell, Ariel L. Escobar, Néstor J. Oviedo
bioRxiv 2021.05.16.444365; doi: https://doi.org/10.1101/2021.05.16.444365
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Restoration of DNA Integrity and Cell Cycle by Electric Stimulation in Planarian Tissues Damaged by Ionizing Radiation
Devon Davidian, Melanie LeGro, Paul G. Barghouth, Salvador Rojas, Benjamin Ziman, Eli Isael Maciel, David Ardell, Ariel L. Escobar, Néstor J. Oviedo
bioRxiv 2021.05.16.444365; doi: https://doi.org/10.1101/2021.05.16.444365

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