Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death.
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.
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
Rodrigo
R
Meléndez García
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
David
D
Arredondo Zamarripa
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
Edith
E
Arnold
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
Xarubet
X
Ruiz-Herrera
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
Ramsés
R
Noguez Imm
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
German
G
Baeza Cruz
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
Norma
N
Adán
Institut National de la Santé et de la Recherche Médicale, U1185, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre 94270, France.
Nadine
N
Binart
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
Juan
J
Riesgo-Escovar
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.
Vincent
V
Goffin
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
Benito
B
Ordaz
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
Fernando
F
Peña-Ortega
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
Ataúlfo
A
Martínez-Torres
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
Carmen
C
Clapp
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico. Electronic address: stephaniethebault@gmail.com.
Stéphanie
S
Thebault
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
D011981:Receptors, Prolactin; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D011388:Prolactin; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D005978:Glutathione
Age-related retinal degeneration; Antioxidant; Prolactin; Retinal pigment epithelium; SIRT2; TRPM2 channels