17β-estradiol induces hyperresponsiveness in guinea pig airway smooth muscle by inhibiting the plasma membrane Ca 2+ -ATPase.

Autor: Romero-Martínez BS; Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad No. 3000, Alcaldía de Coyoacán, CP 04510, CDMX, México., Flores-Soto E; Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad No. 3000, Alcaldía de Coyoacán, CP 04510, CDMX, México., Sommer B; Departamento de Investigación en Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias, Calz. De Tlalpan 4502, Col. Sección XVI, Alcaldía de Tlalpan, CP 14080, CDMX, México., Reyes-García J; Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad No. 3000, Alcaldía de Coyoacán, CP 04510, CDMX, México., Arredondo-Zamarripa D; Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad No. 3000, Alcaldía de Coyoacán, CP 04510, CDMX, México., Solís-Chagoyán H; Neurociencia Cognitiva Evolutiva, Centro de Investigación en Ciencias Cognitivas, Universidad Autónoma Del Estado de Morelos, CP 62209, Morelos, México., Lemini C; Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad No. 3000, Alcaldía de Coyoacán, CP 04510, CDMX, México., Rivero-Segura NA; Dirección de Investigación, Instituto Nacional de Geriatría (INGER), Ciudad de México, CP 10200, México., Santiago-de-la-Cruz JA; Dirección de Investigación, Instituto Nacional de Geriatría (INGER), Ciudad de México, CP 10200, México., Pérez-Plascencia C; Unidad de Genómica y Cáncer, Subdirección de Investigación Básica, INCan, SSA, Av. San Fernando 22, Alcaldía de Tlalpan, CP 14080, CDMX, México; Facultad de Estudios Superiores Iztacala, Av. de Los Barrios S/N Los Reyes Ixtacala Tlalnepantla de Baz, Edo. de México, CP 54090, Tlalnepantla de Baz, México., Montaño LM; Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad No. 3000, Alcaldía de Coyoacán, CP 04510, CDMX, México. Electronic address: lmmr@unam.mx.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2024 Sep 01; Vol. 590, pp. 112273. Date of Electronic Publication: 2024 May 18.
DOI: 10.1016/j.mce.2024.112273
Abstrakt: High serum estrogen concentrations are associated with asthma development and severity, suggesting a link between estradiol and airway hyperresponsiveness (AHR). 17β-estradiol (E2) has non-genomic effects via Ca 2+ regulatory mechanisms; however, its effect on the plasma membrane Ca 2+ -ATPases (PMCA1 and 4) and sarcoplasmic reticulum Ca 2+ -ATPase (SERCA) is unknown. Hence, in the present study, we aim to demonstrate if E2 favors AHR by increasing intracellular Ca 2+ concentrations in guinea pig airway smooth muscle (ASM) through a mechanism involving Ca 2+ -ATPases. In guinea pig ASM, Ca 2+ microfluorometry, muscle contraction, and Western blot were evaluated. Then, we performed molecular docking analysis between the estrogens and Ca 2+ ATPases. In tracheal rings, E2 produced AHR to carbachol. In guinea pig myocytes, acute exposure to physiological levels of E2 modified the transient Ca 2+ peak induced by caffeine to a Ca 2+ plateau. The incubation with PMCA inhibitors (lanthanum and carboxyeosin, CE) partially reversed the E2-induced sustained plateau in the caffeine response. In contrast, cyclopiazonic acid (SERCA inhibitor), U-0126 (an inhibitor of ERK 1/2), and choline chloride did not modify the Ca 2+ plateau produced by E2. The mitochondrial uniporter activity and the capacitative Ca 2+ entry were unaffected by E2. In guinea pig ASM, Western blot analysis demonstrated PMCA1 and PMCA4 expression. The results from the docking modeling demonstrate that E2 binds to both plasma membrane ATPases. In guinea pig tracheal smooth muscle, inhibiting the PMCA with CE, induced hyperresponsiveness to carbachol. 17β-estradiol produces hyperresponsiveness by inhibiting the PMCA in the ASM and could be one of the mechanisms responsible for the increase in asthmatic crisis in women.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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