| Autor: |
Ramírez-Barrantes, Ricardo, Carvajal-Zamorano, Karina, Rodriguez, Belen, Cordova, Claudio, Lozano, Carlo, Simon, Felipe, Díaz, Paula, Muñoz, Pablo, Marchant, Ivanny, Latorre, Ramón, Castillo, Karen, Olivero, Pablo |
| Předmět: |
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| Zdroj: |
Frontiers in Physiology; 5/26/2020, Vol. 11, p1-16, 16p |
| Abstrakt: |
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. TRPV1 is sufficient condition for 17β-estradiol resistance against oxidative stress-induced cell death. The cell death induced by oxidative stress could be characterized by a kinetic model of three state: alive, vulnerable and dead. In particular, the transition from alive to vulnerable state involves the depolarization of mitochondrial membrane potential, and the evolution to cell death the activation of caspases. Only in TRPV1 expressing cells, the initial application of 17β-estradiol protects against the irreversible damage triggered by oxidative stress, by inhibition of the transition from alive to vulnerable state. This mechanism includes blocking oxidative stress-dependent mitochondrial depolarization and the activation of caspases 3/7. Furthermore, 17β-estradiol potentiates TRPV1 activity associated with an increased open probability. Despite the relationship between the activation of TRPV1 and the maintenance of the mitochondrial membrane potential should be clarified, it could include the increase of the calcium buffer capacity of the mitochondria and/or the overexpression of anti-apoptotic proteins such as the Bcl-2 family as previously reported. Finally, the 17β-estradiol cell protection was independent of estrogen receptors, and was membrane started and stereospecific. These results support the role of TRPV1 as a 17β-estradiol ionotropic receptor being critical to cell survival. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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