Abstract |
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 Ca(2+) 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.
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Authors | 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 |
Journal | EBioMedicine
(EBioMedicine)
Vol. 7
Pg. 35-49
(May 2016)
ISSN: 2352-3964 [Electronic] Netherlands |
PMID | 27322457
(Publication Type: Journal Article)
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Copyright | Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Receptors, Prolactin
- TRPM Cation Channels
- TRPM2 protein, human
- Prolactin
- SIRT2 protein, human
- Sirtuin 2
- Glutathione
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Topics |
- Aging
(physiology)
- Animals
- Apoptosis
(drug effects)
- Female
- Glutathione
(metabolism)
- Humans
- Male
- Mice
- Prolactin
(genetics, metabolism)
- Receptors, Prolactin
(genetics, metabolism)
- Retinal Pigment Epithelium
(cytology, metabolism)
- Sirtuin 2
(genetics, metabolism)
- TRPM Cation Channels
(genetics, metabolism)
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