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GLUT1 activity contributes to the impairment of PEDF secretion by the RPE

2016-07Journal article Open Access
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dc.contributor.authorCalado, Sofia
dc.contributor.authorAlves, Liliana S.
dc.contributor.authorS, Simão
dc.contributor.authorSilva, Gabriela A.
dc.date.accessioned2017-04-07T15:56:22Z
dc.date.available2017-04-07T15:56:22Z
dc.date.issued2016-07
dc.description.abstractPurpose: In this study, we aimed to understand whether glucose transporter 1 (GLUT1) activity affects the secretion capacity of antiangiogenic factor pigment epithelium-derived factor (PEDF) by the RPE cells, thus explaining the reduction in PEDF levels observed in patients with diabetic retinopathy (DR).Methods: Analysis of GLUT1 expression, localization, and function was performed in vitro in RPE cells (D407) cultured with different glucose concentrations, corresponding to non-diabetic (5 mM of glucose) and diabetic (25 mM of glucose) conditions, further subjected to normoxia or hypoxia. The expression of PEDF was also evaluated in the secretome of the cells cultured in these conditions. Analysis of GLUT1 and PEDF expression was also performed in vivo in the RPE of Ins2(Akita) diabetic mice and age-matched wild-type (WT) controls.Results: We observed an increase in GLUT1 under hypoxia in a glucose-dependent manner, which we found to be directly associated with the translocation and stabilization of GLUT1 in the cell membrane. This stabilization led to an increase in glucose uptake by RPE cells. This increase was followed by a decrease in PEDF expression in RPE cells cultured in conditions that simulated DR. Compared with non-diabetic WT mice, the RPE of Ins2Akita mice showed increased GLUT1 overexpression with a concomitant decrease in PEDF expression.Conclusions: Collectively, our data show that expression of GLUT1 is stimulated by hyperglycemia and low oxygen supply, and this overexpression was associated with increased activity of GLUT1 in the cell membrane that contributes to the impairment of the RPE secretory function of PEDF.
dc.description.sponsorshipPest-OE/EQB/LA0023 /2013; PIRG05-GA-2009–249314–EyeSee; EXPL-BIMMEC-1433–2013
dc.identifier.issn1090-0535
dc.identifier.urihttp://hdl.handle.net/10400.1/9395
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMolecular Vision
dc.relationMULTIFACTORIAL APPROACH TO NON-VIRAL GENE THERAPY: DEVELOPMENT OF AN EFFICIENT SYSTEM FOR THE RETINA
dc.relationiNOVA4Health - Programme in Translational Medicine (iBET, CEDOC/FCM, IPOLFG and ITQB)
dc.relation.isbasedonWOS:000384564900001
dc.titleGLUT1 activity contributes to the impairment of PEDF secretion by the RPE
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMULTIFACTORIAL APPROACH TO NON-VIRAL GENE THERAPY: DEVELOPMENT OF AN EFFICIENT SYSTEM FOR THE RETINA
oaire.awardTitleiNOVA4Health - Programme in Translational Medicine (iBET, CEDOC/FCM, IPOLFG and ITQB)
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F76873%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F78404%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04462%2F2013/PT
oaire.citation.endPage770
oaire.citation.startPage761
oaire.citation.titleMolecular Vision
oaire.citation.volume22
oaire.fundingStreamSFRH
oaire.fundingStream6817 - DCRRNI ID
person.familyNameCalado
person.familyNameSimao
person.givenNameSofia
person.givenNameSonia
person.identifier.ciencia-id7C1A-91BA-B6A0
person.identifier.orcid0000-0001-5509-4145
person.identifier.orcid0000-0002-0245-0633
person.identifier.ridK-2202-2016
person.identifier.scopus-author-id56426215600
person.identifier.scopus-author-id24067982400
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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