Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death
Rodrigo Meléndez García,
David Arredondo Zamarripa,
Edith Arnold,
Xarubet Ruiz-Herrera,
Ramsés Noguez Imm,
German Baeza Cruz,
Norma Adán,
Nadine Binart,
Juan Riesgo-Escovar,
Vincent Goffin,
Benito Ordaz,
Fernando Peña-Ortega,
Ataúlfo Martínez-Torres,
Carmen Clapp,
Stéphanie Thebault
Affiliations
Rodrigo Meléndez García
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
David Arredondo Zamarripa
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
Edith Arnold
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
Xarubet Ruiz-Herrera
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
Ramsés Noguez Imm
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
German Baeza Cruz
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
Norma Adán
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
Nadine Binart
Institut National de la Santé et de la Recherche Médicale, U1185, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre 94270, France
Juan Riesgo-Escovar
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
Vincent Goffin
Institut National de la Santé et de la Recherche Médicale, U1151, Institut Necker Enfants Malades, Université Paris-Descartes, Faculté de Médecine, Sorbonne Paris Cité, 75014, France
Benito Ordaz
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
Fernando Peña-Ortega
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
Ataúlfo Martínez-Torres
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
Carmen Clapp
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
Stéphanie Thebault
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico
The identification of pathways necessary for retinal pigment epithelium (RPE) function is fundamental to uncover therapies for blindness. Prolactin (PRL) receptors are expressed in the retina, but nothing is known about the role of PRL in RPE. Using the adult RPE 19 (ARPE-19) human cell line and mouse RPE, we identified the presence of PRL receptors and demonstrated that PRL is necessary for RPE cell survival via anti-apoptotic and antioxidant actions. PRL promotes the antioxidant capacity of ARPE-19 cells by reducing glutathione. It also blocks the hydrogen peroxide-induced increase in deacetylase sirtuin 2 (SIRT2) expression, which inhibits the TRPM2-mediated intracellular Ca2+ rise associated with reduced survival under oxidant conditions. RPE from PRL receptor-null (prlr−/−) mice showed increased levels of oxidative stress, Sirt2 expression and apoptosis, effects that were exacerbated in animals with advancing age. These observations identify PRL as a regulator of RPE homeostasis.
