Latorre, RamónRamónLatorreMarchant, IvannyIvannyMarchantMuñoz, PabloPabloMuñozOlivero, PabloPabloOliveroRicardo Ramírez-BarrantesKarina Carvajal-ZamoranoBelén RodríguezClaudio CórdovaCarlo LozanoFelipe SimónPaula DíazKaren Castillo2025-08-252025-08-252020-05-2610.3389/fphys.2020.004442-s2.0-85086251047https://cris-uv-2.scimago.es/handle/123456789/3535WOS:00054193740000117β-estradiol is a neuronal survival factor against oxidative stress that triggers its protective effect even in the absence of classical estrogen receptors. The polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channel has been proposed as a steroid receptor implied in tissue protection against oxidative damage. We show here that TRPV1 is sufficient condition for 17β-estradiol to enhance metabolic performance in injured cells. Specifically, in TRPV1 expressing cells, the application of 17β-estradiol within the first 3 h avoided H₂O₂-dependent mitochondrial depolarization and the activation of caspase 3/7 protecting against the irreversible damage triggered by H₂O₂. Furthermore, 17β-estradiol potentiates TRPV1 single channel activity associated with an increased open probability. This effect was not observed after the application of 17α-estradiol. We explored the TRPV1-Estrogen relationship also in primary culture of hippocampal-derived neurons and observed that 17β-estradiol cell protection against H₂O₂-induced damage was independent of estrogen receptors pathway activation, membrane started and stereospecific. These results support the role of TRPV1 as a 17β-estradiol-activated ionotropic membrane receptor coupling with mitochondrial function and cell survival.enacceso abiertoPhysiologyarticle