Ramírez-Barrantes et al. TRPV1 Contribution in 17β-Estradiol Cell Protection GRAPHICAL ABSTRACT | 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.

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