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dc.contributor.author
Hanschmann, Eva Maria
dc.contributor.author
Wilms, Christina
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Falk, Lisa
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Holubiec, Mariana Ines
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Mennel, Stefan
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Lillig, Christopher Horst
dc.contributor.author
Godoy, José Rodrigo
dc.date.available
2023-08-29T18:46:53Z
dc.date.issued
2022-08
dc.identifier.citation
Hanschmann, Eva Maria; Wilms, Christina; Falk, Lisa; Holubiec, Mariana Ines; Mennel, Stefan; et al.; Cytosolic glutaredoxin 1 is upregulated in AMD and controls retinal pigment epithelial cells proliferation via β-catenin; Academic Press Inc Elsevier Science; Biochemical and Biophysical Research Communications; 618; 8-2022; 24-29
dc.identifier.issn
0006-291X
dc.identifier.uri
http://hdl.handle.net/11336/209827
dc.description.abstract
Thioredoxin (Trx) family proteins are key players in redox signaling. Here, we have analyzed glutaredoxin (Grx) 1 and Grx2 in age-related macular degeneration (AMD) and in retinal pigment epithelial (ARPE-19) cells. We hypothesized that these redoxins regulate cellular functions and signaling circuits such as cell proliferation, Wnt signaling and VEGF release that have been correlated to the pathophysiology of AMD. ARPE-19 cells were transfected with specific siRNAs to silence the expression of Grx1 and Grx2 and were analyzed for proliferation/viability, migration capacity, β-catenin activation, and VEGF release. An active site-mutated C-X-X-S Grx1 was utilized to trap interacting proteins present in ARPE-19 cell extracts. In both, AMD retinas and in ARPE-19 cells incubated under hypoxia/reoxygenation conditions, Grx1 showed an increased nuclear localization. Grx1-silenced ARPE-19 cells showed a significantly reduced proliferation and migration rate. Our trapping approach showed that Grx1 interacts with β-catenin in a dithiol-disulfide exchange reaction. Knock-down of Grx1 led to a reduction in both total and active β-catenin levels. These findings add redox control to the regulatory mechanisms of β-catenin signaling in the retinal pigment epithelium and open the door to novel therapeutic approaches in AMD that is currently treated with VEGF-inhibitors.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Academic Press Inc Elsevier Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
AGE-RELATED MACULAR DEGENERATION
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ARPE-19
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GLUTAREDOXIN
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HYPOXIA
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Β-CATENIN
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Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Cytosolic glutaredoxin 1 is upregulated in AMD and controls retinal pigment epithelial cells proliferation via β-catenin
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-07-10T11:48:44Z
dc.journal.volume
618
dc.journal.pagination
24-29
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Hanschmann, Eva Maria. Heinrich-Heine University; Alemania. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG);
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Fil: Wilms, Christina. Heinrich-Heine University; Alemania
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Fil: Falk, Lisa. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG);
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Fil: Holubiec, Mariana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
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Fil: Mennel, Stefan. Hospital Feldkirch; Austria
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Fil: Lillig, Christopher Horst. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG);
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Fil: Godoy, José Rodrigo. Long Island University; Estados Unidos
dc.journal.title
Biochemical and Biophysical Research Communications
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006291X22008750
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bbrc.2022.06.030
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