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 mou...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-05-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396416301359 |
| _version_ | 1818601860178640896 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Rodrigo Meléndez García |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T12:58:05Z |
| format | Article |
| id | doaj.art-6b228543c3864e4aa2c8d54a81dbc4ff |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-16T12:58:05Z |
| publishDate | 2016-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-6b228543c3864e4aa2c8d54a81dbc4ff2022-12-21T22:30:57ZengElsevierEBioMedicine2352-39642016-05-017C354910.1016/j.ebiom.2016.03.048Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell deathRodrigo Meléndez García0David Arredondo Zamarripa1Edith Arnold2Xarubet Ruiz-Herrera3Ramsés Noguez Imm4German Baeza Cruz5Norma Adán6Nadine Binart7Juan Riesgo-Escovar8Vincent Goffin9Benito Ordaz10Fernando Peña-Ortega11Ataúlfo Martínez-Torres12Carmen Clapp13Stéphanie Thebault14Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstitut National de la Santé et de la Recherche Médicale, U1185, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre 94270, FranceInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstitut National de la Santé et de la Recherche Médicale, U1151, Institut Necker Enfants Malades, Université Paris-Descartes, Faculté de Médecine, Sorbonne Paris Cité, 75014, FranceInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, MexicoThe 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.http://www.sciencedirect.com/science/article/pii/S2352396416301359Age-related retinal degenerationProlactinAntioxidantSIRT2TRPM2 channelsRetinal pigment epithelium |
| spellingShingle | 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 Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death EBioMedicine Age-related retinal degeneration Prolactin Antioxidant SIRT2 TRPM2 channels Retinal pigment epithelium |
| title | Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death |
| title_full | Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death |
| title_fullStr | Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death |
| title_full_unstemmed | Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death |
| title_short | Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death |
| title_sort | prolactin protects retinal pigment epithelium by inhibiting sirtuin 2 dependent cell death |
| topic | Age-related retinal degeneration Prolactin Antioxidant SIRT2 TRPM2 channels Retinal pigment epithelium |
| url | http://www.sciencedirect.com/science/article/pii/S2352396416301359 |
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