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Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death.

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.
AuthorsRodrigo 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
JournalEBioMedicine (EBioMedicine) Vol. 7 Pg. 35-49 (May 2016) ISSN: 2352-3964 [Electronic] Netherlands
PMID27322457 (Publication Type: Journal Article)
CopyrightCopyright © 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
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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