Artículo
Cytosolic glutaredoxin 1 is upregulated in AMD and controls retinal pigment epithelial cells proliferation via β-catenin
Hanschmann, Eva Maria; Wilms, Christina; Falk, Lisa; Holubiec, Mariana Ines
; Mennel, Stefan; Lillig, Christopher Horst; Godoy, José Rodrigo
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
08/2022
Editorial:
Academic Press Inc Elsevier Science
Revista:
Biochemical and Biophysical Research Communications
ISSN:
0006-291X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
AGE-RELATED MACULAR DEGENERATION
,
ARPE-19
,
GLUTAREDOXIN
,
HYPOXIA
,
Β-CATENIN
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Identificadores
Colecciones
Articulos(IBIOBA - MPSP)
Articulos de INST. D/INV.EN BIOMED.DE BS AS-CONICET-INST. PARTNER SOCIEDAD MAX PLANCK
Articulos de INST. D/INV.EN BIOMED.DE BS AS-CONICET-INST. PARTNER SOCIEDAD MAX PLANCK
Citación
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
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