RT Journal Article
SR Electronic
T1 Restoration of DNA Integrity and Cell Cycle by Electric Stimulation in Planarian Tissues Damaged by Ionizing Radiation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.16.444365
DO 10.1101/2021.05.16.444365
A1 Davidian, Devon
A1 LeGro, Melanie
A1 Barghouth, Paul G.
A1 Rojas, Salvador
A1 Ziman, Benjamin
A1 Maciel, Eli Isael
A1 Ardell, David
A1 Escobar, Ariel L.
A1 Oviedo, Néstor J.
YR 2021
UL http://biorxiv.org/content/early/2021/05/17/2021.05.16.444365.abstract
AB 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 StatementThe authors have declared no competing interest.