AG 205, a progesterone receptor membrane component 1 antagonist, ablates progesterone's ability to block oxidative stress-induced apoptosis of human granulosa/luteal cells.

Will, Erica Anspach; Liu, Xiufang; Peluso, John J

AG 205, a progesterone receptor membrane component 1 antagonist, ablates progesterone's ability to block oxidative stress-induced apoptosis of human granulosa/luteal cells.

Will, Erica Anspach; Liu, Xiufang; Peluso, John J.

Afiliación

Will EA; Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, Connecticut, USA.
Liu X; The Center for Advanced Reproductive Services, Farmington Connecticut, USA.
Peluso JJ; Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut, USA.

Biol Reprod ; 96(4): 843-854, 2017 Apr 01.

Article en En | MEDLINE | ID: mdl-28371915

RESUMEN

The present studies were designed to determine whether progesterone (P4)-progesterone receptor membrane component 1 (PGRMC1) signaling is able to attenuate the apoptotic effects of oxidative stress induced by hydrogen peroxide (H2O2). To achieve this goal, freshly isolated human granulosa/luteal cells were maintained in culture. After several passages, the cells were treated with H2O2, which induced apoptosis within 2.5 h, while simultaneous treatment with P4 attenuated the apoptotic action of H2O2. AG 205, a PGRMC1 antagonist, eliminated P4's ability to prevent H2O2-induced apoptosis. AG 205 neither affected PGRMC1's cytoplasmic localization nor its interaction with PGRMC2, but appeared to reduce its presence within the nucleus. AG 205 also (1) increased the monomeric and decreased the higher molecular weight forms of PGRMC1 (i.e., dimers/oligomers) and (2) altered the expression of several genes involved in apoptosis. The most dramatic change was an approximate 8-fold increase in Harakiri (Hrk) mRNA. However, AG 205 did not induce apoptosis in the absence of H2O2. Taken together, these observations suggest that the higher molecular weight forms of PGRMC1 likely account in part for PGRMC1's ability to suppress the expression of Hrk. Harakiri is a BH-3 only member of the B-cell lymphoma 2 (BCL2) family that promotes apoptosis by binding to and antagonizing the antiapoptotic action of BCL2- and BCL2-like proteins. It is likely then that PGRMC1's ability to suppress Hrk is part of the mechanism through which P4-PGRMC1 signaling preserves the viability of human granulosa/luteal cells.

Asunto(s)

Apoptosis/fisiología; Células de la Granulosa/fisiología; Indoles/farmacología; Células Lúteas/fisiología; Proteínas de la Membrana/antagonistas & inhibidores; Estrés Oxidativo/efectos de los fármacos; Progesterona/farmacología; Receptores de Progesterona/antagonistas & inhibidores; Animales; Apoptosis/efectos de los fármacos; Supervivencia Celular; Femenino; Células de la Granulosa/efectos de los fármacos; Células Lúteas/efectos de los fármacos

Palabras clave

PGRMC1; PGRMC2; apoptosis; granulosa cells; progesterone

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Progesterona / Receptores de Progesterona / Apoptosis / Estrés Oxidativo / Células de la Granulosa / Indoles / Células Lúteas / Proteínas de la Membrana Límite: Animals Idioma: En Revista: Biol Reprod Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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