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dc.contributor.author
Marazita, Mariela Claudia
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dc.contributor.author
Dugour, Andrea Vanesa
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dc.contributor.author
Marquioni Ramella, Melisa Daniela
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dc.contributor.author
Figueroa, J.M.
dc.contributor.author
Suburo, Angela Maria
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dc.date.available
2018-04-03T14:28:57Z
dc.date.issued
2016-04
dc.identifier.citation
Marazita, Mariela Claudia; Dugour, Andrea Vanesa; Marquioni Ramella, Melisa Daniela; Figueroa, J.M.; Suburo, Angela Maria; Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: Implications for Age-related Macular Degeneration; ELSEVIER BV; Redox Biology; 7; 87; 4-2016; 78-87
dc.identifier.issn
2213-2317
dc.identifier.uri
http://hdl.handle.net/11336/40487
dc.description.abstract
AbstractOxidative stress has a critical role in the pathogenesis of Age-related Macular Degeneration (AMD), a multifactorial disease that includes age, gene variants of complement regulatory proteins and smoking as the main risk factors. Stress-induced premature cellular senescence (SIPS) is postulated to contribute to this condition. In this study, we hypothesized that oxidative damage, promoted by endogenous or exogenous sources, could elicit a senescence response in RPE cells, which would in turn dysregulate the expression of major players in AMD pathogenic mechanisms. We showed that exposure of a human RPE cell line (ARPE-19) to a cigarette smoke concentrate (CSC), not only enhanced Reactive Oxygen Species (ROS) levels, but also induced 8-Hydroxydeoxyguanosine-immunoreactive (8-OHdG) DNA lesions and phosphorylated-Histone 2AX-immunoreactive (p-H2AX) nuclear foci. CSC-nuclear damage was followed by premature senescence as shown by positive senescence associated-β-galactosidase (SA-β-Gal) staining, and p16INK4a and p21Waf-Cip1 protein upregulation. N-acetylcysteine (NAC) treatment, a ROS scavenger, decreased senescence markers, thus supporting the role of oxidative damage in CSC-induced senescence activation. ARPE-19 senescent cultures were also established by exposure to hydrogen peroxide (H2O2), which is an endogenous stress source produced in the retina under photo-oxidation conditions. Senescent cells upregulated the proinflammatory cytokines IL-6 and IL-8, the main markers of the senescence-associated secretory phenotype (SASP). Most important, we show for the first time that senescent ARPE-19 cells upregulated vascular endothelial growth factor (VEGF) and simultaneously downregulated complement factor H (CFH) expression. Since both phenomena are involved in AMD pathogenesis, our results support the hypothesis that SIPS could be a principal player in the induction and progression of AMD. Moreover, they would also explain the striking association of this disease with cigarette smoking.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
ELSEVIER BV
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Cellular Senescence
dc.subject
Amd
dc.subject
Sasp
dc.subject
Dna Damage
dc.subject
Oxidative Dna Damage
dc.subject
Cigarette Smoke
dc.subject
Retinal Pigment Epithelial Cells
dc.subject.classification
Otras Ciencias Biológicas
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: Implications for Age-related Macular Degeneration
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-03-27T15:17:25Z
dc.journal.volume
7
dc.journal.number
87
dc.journal.pagination
78-87
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Pensilvania
dc.description.fil
Fil: Marazita, Mariela Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Dugour, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Pablo Cassará; Argentina
dc.description.fil
Fil: Marquioni Ramella, Melisa Daniela. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Figueroa, J.M.. Fundación Pablo Cassará; Argentina
dc.description.fil
Fil: Suburo, Angela Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.journal.title
Redox Biology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.redox.2015.11.011
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2213231715300136
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