Early bioelectric activities mediate redox-modulated regeneration.
Reactive oxygen species (ROS) and electric currents modulate regeneration; however, the interplay between biochemical and biophysical signals during regeneration remains poorly understood. We investigate the interactions between redox and bioelectric activities during tail regeneration in Xenopus laevis tadpoles. We show that inhibition of NADPH oxidase-mediated production of ROS, or scavenging or blocking their diffusion into cells, impairs regeneration and consistently regulates the dynamics of membrane potential, transepithelial potential (TEP) and electric current densities (JI) during regeneration. Depletion of ROS mimics the altered TEP and JIobserved in the non-regenerative refractory period. Short-term application of hydrogen peroxide (H2O2) rescues (from depleted ROS) and induces (from the refractory period) regeneration, TEP increase and JIreversal. H2O2is therefore necessary for and sufficient to induce regeneration and to regulate TEP and JIEpistasis assays show that voltage-gated Na+channels act downstream of H2O2to modulate regeneration. Altogether, these results suggest a novel mechanism for regeneration via redox-bioelectric orchestration.
Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, CA 95817, USA fdasilvaferreira@ucdavis.edu minzhao@ucdavis.edu.|Departamento de Biologia, Centro de Biologia Molecular e Ambiental (CBMA), Universidade do Minho, Braga 4710, Portugal.
Fernando
F
Ferreira
Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, CA 95817, USA.
Guillaume
G
Luxardi
Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, CA 95817, USA.
Brian
B
Reid
Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, CA 95817, USA fdasilvaferreira@ucdavis.edu minzhao@ucdavis.edu.|Department of Ophthalmology, Institute for Regenerative Cures, University of California, Davis, CA 95817, USA.
Min
0000-0002-2500-3035
M
Zhao
D000818:Animals; D055724:Electrophysiological Phenomena / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D007814:Larva / Q000254:growth & development*; D008564:Membrane Potentials / Q000502:physiology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D012038:Regeneration / Q000502:physiology*; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*; D014982:Xenopus laevis / Q000254:growth & development*
D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases
Electric current density; Membrane potential; NADPH oxidases; Reactive oxygen species; Regeneration; Transepithelial potential; Voltage-gated Na+ channels; Xenopus laevis