TRPV1-Estradiol Stereospecific Relationship Underlies Cell Survival in Oxidative Cell Death

Frontiers in Physiology

Karen Castillo¹  Karina Carvajal-Zamorano¹  Ramón Latorre¹  Pablo Olivero²  Carlo Lozano²  Ivanny Marchant²  Pablo Muñoz³  Ricardo Ramírez-Barrantes⁴  Claudio Cordova⁶  Belen Rodriguez⁶  Paula Díaz⁶  Felipe Simon⁷ 

[1] Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile;Centro Interoperativo en Ciencias Odontológicas y Médicas, Universidad de Valparaíso, Valparaíso, Chile;Centro de Neurología Traslacional, Facultad de Medicina, Universidad de Valparaíso, Valparaíso, Chile;Escuela de Tecnología Médica, Universidad Andrés Bello, Viña del Mar, Chile;Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile;Laboratorio de Estructura y Función Celular, Escuela de Medicina, Facultad de Medicina, Universidad de Valparaíso, Valparaíso, Chile;Millennium Nucleus of Ion Channels-Associated Diseases (MiNICAD), Universidad de Chile, Santiago, Chile;

关键词: TRPV1;    17β-estradiol;    cell death;    membrane receptor;    neuroprotection;   

DOI  :  10.3389/fphys.2020.00444

来源: DOAJ

【 摘 要 】

17β-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.

【 授权许可】

Unknown