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TMEM16A inhibition impedes capacitation and acquisition of hyperactivated motility in guinea pig sperm.
Cordero-Martínez, Joaquín; Reyes-Miguel, Tania; Rodríguez-Páez, Lorena; Garduño-Siciliano, Leticia; Maldonado-García, Deneb; Roa-Espitia, Ana L; Hernández-González, Enrique O.
Afiliação
  • Cordero-Martínez J; Departamento de Biología Celular, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional. Av. Instituto Politécnico Nacional, San Pedro Zacatenco, Del. Gustavo A. Madero, México City, Mexico.
  • Reyes-Miguel T; Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Prolongación Manuel Carpio y Plan de Ayala s/n Col, Santo Tomás, Del. Miguel Hidalgo, México City, Mexico.
  • Rodríguez-Páez L; Departamento de Biología Celular, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional. Av. Instituto Politécnico Nacional, San Pedro Zacatenco, Del. Gustavo A. Madero, México City, Mexico.
  • Garduño-Siciliano L; Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Prolongación Manuel Carpio y Plan de Ayala s/n Col, Santo Tomás, Del. Miguel Hidalgo, México City, Mexico.
  • Maldonado-García D; Laboratorio de Toxicología de Productos Naturales. Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Prol. Av. Wilfrido Massieu s/n, esq. Manuel L. Stampa, Col. Unidad Profesional Adolfo López Mateos, Del. Gustavo A. Madero, México City, Mexico.
  • Roa-Espitia AL; Departamento de Biología Celular, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional. Av. Instituto Politécnico Nacional, San Pedro Zacatenco, Del. Gustavo A. Madero, México City, Mexico.
  • Hernández-González EO; Departamento de Biología Celular, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional. Av. Instituto Politécnico Nacional, San Pedro Zacatenco, Del. Gustavo A. Madero, México City, Mexico.
J Cell Biochem ; 119(7): 5944-5959, 2018 07.
Article em En | MEDLINE | ID: mdl-29600587
Ca2+ -activated Cl- channels (CaCCs) are anionic channels that regulate many important physiological functions associated with chloride and calcium flux in some somatic cells. The molecular identity of CaCCs was revealed to be TMEM16A and TMEM16B (also known as Anoctamin or ANO1 and ANO2, respectively) in all eukaryotes. A recent study suggests the presence of TMEM16A in human sperm and a relationship with the rhZP-induced acrosome reaction. However, to the best of our knowledge, little is known about the role of TMEM16A in other spermatic processes such as capacitation or motility. In this study, we evaluated the effects of two TMEM16A antagonists on capacitation, acrosome reaction, and motility in guinea pig sperm; these antagonists were T16Ainh-A01, belonging to a second generation of potent antagonists of TMEM16A, and niflumic acid (NFA), a well-known antagonist of TMEM16A (CaCCs). First of all, we confirmed that the absence of Cl- in the capacitation medium changes motility parameters, capacitation, and the progesterone-induced acrosome reaction. Using a specific antibody, TMEM16A was found as a protein band of ∼120 kDa, which localization was in the apical crest of the acrosome and the middle piece of the flagellum. Inhibition of TMEM16A by T16Ainh-A01 affected sperm physiology by reducing capacitation, blocking the progesterone-induced acrosome reaction under optimal capacitation conditions, inhibiting progressive motility, and the acquisition of hyperactivated motility, diminishing [Ca2+ ]i, and increasing [Cl- ]i. These changes in sperm kinematic parameters provide new evidence of the important role played by TMEM16A in the production of sperm capable of fertilizing oocytes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirimidinas / Capacitação Espermática / Motilidade dos Espermatozoides / Tiazóis / Anoctamina-1 Limite: Animals Idioma: En Revista: J Cell Biochem Ano de publicação: 2018 Tipo de documento: Article País de afiliação: México País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirimidinas / Capacitação Espermática / Motilidade dos Espermatozoides / Tiazóis / Anoctamina-1 Limite: Animals Idioma: En Revista: J Cell Biochem Ano de publicação: 2018 Tipo de documento: Article País de afiliação: México País de publicação: Estados Unidos