HERPUD1 protects against oxidative stress-induced apoptosis through downregulation of the inositol 1,4,5-trisphosphate receptor
Author
dc.contributor.author
Paredes, Felipe
Author
dc.contributor.author
Parra, Valentina
Author
dc.contributor.author
Torrealba, Natalia
Author
dc.contributor.author
Navarro Márquez, Mario F.
Author
dc.contributor.author
Gatica, Damián
Author
dc.contributor.author
Bravo Sagua, Roberto
Author
dc.contributor.author
Troncoso, Rodrigo
Author
dc.contributor.author
Pennanen, Christian
Author
dc.contributor.author
Quiroga, Clara
Author
dc.contributor.author
Chiong Lay, Mario
Author
dc.contributor.author
Caesar, Christa
Author
dc.contributor.author
Taylor, W. Robert
Author
dc.contributor.author
Molgó, Jordi
Author
dc.contributor.author
San Martín, Alejandra
Author
dc.contributor.author
Jaimovich Pérez, Enrique
Author
dc.contributor.author
Lavandero González, Sergio
Admission date
dc.date.accessioned
2016-01-27T20:06:45Z
Available date
dc.date.available
2016-01-27T20:06:45Z
Publication date
dc.date.issued
2016
Cita de ítem
dc.identifier.citation
Free Radical Biology and Medicine 90 (2016) 206–218
en_US
Identifier
dc.identifier.other
DOI: 10.1016/j.freeradbiomed.2015.11.024
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/136812
General note
dc.description
Artículo de publicación ISI
en_US
Abstract
dc.description.abstract
Homocysteine-inducible, endoplasmic reticulum (ER) stress-inducible, ubiquitin-like domain member 1 (HERPUD1), an ER resident protein, is upregulated in response to ER stress and Ca2(+) homeostasis deregulation. HERPUD1 exerts cytoprotective effects in various models, but its role during oxidative insult remains unknown. The aim of this study was to investigate whether HERPUD1 contributes to cytoprotection in response to redox stress and participates in mediating stress-dependent signaling pathways. Our data showed that HERPUD1 protein levels increased in HeLa cells treated for 30 min with H2O2 or angiotensin II and in aortic tissue isolated from mice treated with angiotensin II for 3 weeks. Cell death was higher in HERPUD1 knockdown (sh-HERPUD1) HeLa cells treated with H2O2 in comparison with control (sh-Luc) HeLa cells. This effect was abolished by the intracellular Ca2(+) chelating agent BAPTA-AM or the inositol 1,4,5-trisphosphate receptor (ITPR) antagonist xestospongin B, suggesting that the response to H2O2 was dependent on intracellular Ca2(+) stores and the ITPR. Ca2(+) kinetics showed that sh-HERPUD1 HeLa cells exhibited greater and more sustained cytosolic and mitochondrial Ca2(+) increases than sh-Luc HeLa cells. This higher sensitivity of sh-HERPUD1 HeLa cells to H2O2 was prevented with the mitochondrial permeability transition pore inhibitor cyclosporine A. We concluded that the HERPUD1-mediated cytoprotective effect against oxidative stress depends on the ITPR and Ca2(+) transfer from the ER to mitochondria.
en_US
Patrocinador
dc.description.sponsorship
CONICYT: FONDECYT
1120212
11140470
11130285
3130749
FONDAP
15130011
National Institutes of Health
HL113167
CONICYT Chile