Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy

Autores
García, Isabel Mercedes; Altamirano, Berta Liliana; Mazzei, Luciana Jorgelina; Fornes, Miguel Walter; Molina, Marisa Nile; Ferder, León; Manucha, Walter Ariel Fernando
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Vitamin D slows the progression of chronic kidney disease. Furthermore, activators of vitamin D receptors (VDR) have suppressant effects on the renin-angiotensin system, as well as anti-inflammatory and antifibrotic actions. This study aimed to evaluate the cytoprotective effects of paricalcitol, a VDR activator, at the mitochondrial level using an obstructive nephropathy model [unilateral ureteral obstruction (UUO)]. Rats subjected to UUO and controls were treated daily with vehicle or paricalcitol. The control group underwent a sham surgery. The treatment was done for 15 days (30 ng/kg). The following were determined: biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; VDR, AT(1) receptor, and NADPH oxidase 4 expression; and NADPH oxidase activity (in total and in mitochondrial fractions from the renal cortex). VDR activation prevented fibrosis (20 ± 5 vs. 60 ± 10%) and the number of TUNEL-positive apoptotic cells (10 ± 3 vs. 25 ± 4) in UUO. Biochemical, histological, and molecular studies suggest mitochondrial injury. Electron microscopy revealed in UUO electronically luminous material in the nucleus. Some mitochondria were increased in size and contained dilated crests and larger than normal spaces in their interiors. These changes were not present with paricalcitol treatment. Additionally, high AT(1)-receptor mRNA and NADPH activity was reverted in mitochondrial fractions from obstructed paricalcitol-treated animals (0.58 ± 0.06 vs. 0.95 ± 0.05 relative densitometry units and 9,000 ± 800 vs. 15,000 ± 1,000 relative fluorescence units·μg protein(-1)·min(-1), respectively). These changes were consistent with an improvement in VDR expression (0.75 ± 0.05 vs. 0.35 ± 0.04 relative densitometry units). These results suggest that paricalcitol confers a protective effect and reveal, as well, a possible AT(1) receptor-dependent protective effect that occurs at the mitochondrial level.
Fil: García, Isabel Mercedes. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Altamirano, Berta Liliana. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Fornes, Miguel Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Molina, Marisa Nile. Universidad "Juan Agustín Maza". Facultad de Farmacia y Bioquímica; Argentina
Fil: Ferder, León. Ponce School Of Medicine; Puerto Rico
Fil: Manucha, Walter Ariel Fernando. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Materia
Vitamin D Receptor
Obstructive Nephropathy
Paricalcitol
Mitochondria
At1 Receptors
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/81956
Acceder
id CONICETDig_eb929cc6454d98f0f0374f7e56a203ba
oai_identifier_str oai:ri.conicet.gov.ar:11336/81956
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathyGarcía, Isabel MercedesAltamirano, Berta LilianaMazzei, Luciana JorgelinaFornes, Miguel WalterMolina, Marisa NileFerder, LeónManucha, Walter Ariel FernandoVitamin D ReceptorObstructive NephropathyParicalcitolMitochondriaAt1 Receptorshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Vitamin D slows the progression of chronic kidney disease. Furthermore, activators of vitamin D receptors (VDR) have suppressant effects on the renin-angiotensin system, as well as anti-inflammatory and antifibrotic actions. This study aimed to evaluate the cytoprotective effects of paricalcitol, a VDR activator, at the mitochondrial level using an obstructive nephropathy model [unilateral ureteral obstruction (UUO)]. Rats subjected to UUO and controls were treated daily with vehicle or paricalcitol. The control group underwent a sham surgery. The treatment was done for 15 days (30 ng/kg). The following were determined: biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; VDR, AT(1) receptor, and NADPH oxidase 4 expression; and NADPH oxidase activity (in total and in mitochondrial fractions from the renal cortex). VDR activation prevented fibrosis (20 ± 5 vs. 60 ± 10%) and the number of TUNEL-positive apoptotic cells (10 ± 3 vs. 25 ± 4) in UUO. Biochemical, histological, and molecular studies suggest mitochondrial injury. Electron microscopy revealed in UUO electronically luminous material in the nucleus. Some mitochondria were increased in size and contained dilated crests and larger than normal spaces in their interiors. These changes were not present with paricalcitol treatment. Additionally, high AT(1)-receptor mRNA and NADPH activity was reverted in mitochondrial fractions from obstructed paricalcitol-treated animals (0.58 ± 0.06 vs. 0.95 ± 0.05 relative densitometry units and 9,000 ± 800 vs. 15,000 ± 1,000 relative fluorescence units·μg protein(-1)·min(-1), respectively). These changes were consistent with an improvement in VDR expression (0.75 ± 0.05 vs. 0.35 ± 0.04 relative densitometry units). These results suggest that paricalcitol confers a protective effect and reveal, as well, a possible AT(1) receptor-dependent protective effect that occurs at the mitochondrial level.Fil: García, Isabel Mercedes. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Altamirano, Berta Liliana. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Fornes, Miguel Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Molina, Marisa Nile. Universidad "Juan Agustín Maza". Facultad de Farmacia y Bioquímica; ArgentinaFil: Ferder, León. Ponce School Of Medicine; Puerto RicoFil: Manucha, Walter Ariel Fernando. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaAmerican Physiological Society2012-04-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/81956García, Isabel Mercedes; Altamirano, Berta Liliana; Mazzei, Luciana Jorgelina; Fornes, Miguel Walter; Molina, Marisa Nile; et al.; Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy; American Physiological Society; American Journal Of Physiology-renal Physiology; 302; 12; 4-4-2012; 1565-16051931-857XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajprenal.00617.2011info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/ajprenal.00617.2011info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:42:25Zoai:ri.conicet.gov.ar:11336/81956instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:42:25.409CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy
title Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy
spellingShingle Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy
García, Isabel Mercedes
Vitamin D Receptor
Obstructive Nephropathy
Paricalcitol
Mitochondria
At1 Receptors
title_short Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy
title_full Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy
title_fullStr Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy
title_full_unstemmed Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy
title_sort Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy
dc.creator.none.fl_str_mv García, Isabel Mercedes
Altamirano, Berta Liliana
Mazzei, Luciana Jorgelina
Fornes, Miguel Walter
Molina, Marisa Nile
Ferder, León
Manucha, Walter Ariel Fernando
author García, Isabel Mercedes
author_facet García, Isabel Mercedes
Altamirano, Berta Liliana
Mazzei, Luciana Jorgelina
Fornes, Miguel Walter
Molina, Marisa Nile
Ferder, León
Manucha, Walter Ariel Fernando
author_role author
author2 Altamirano, Berta Liliana
Mazzei, Luciana Jorgelina
Fornes, Miguel Walter
Molina, Marisa Nile
Ferder, León
Manucha, Walter Ariel Fernando
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Vitamin D Receptor
Obstructive Nephropathy
Paricalcitol
Mitochondria
At1 Receptors
topic Vitamin D Receptor
Obstructive Nephropathy
Paricalcitol
Mitochondria
At1 Receptors
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Vitamin D slows the progression of chronic kidney disease. Furthermore, activators of vitamin D receptors (VDR) have suppressant effects on the renin-angiotensin system, as well as anti-inflammatory and antifibrotic actions. This study aimed to evaluate the cytoprotective effects of paricalcitol, a VDR activator, at the mitochondrial level using an obstructive nephropathy model [unilateral ureteral obstruction (UUO)]. Rats subjected to UUO and controls were treated daily with vehicle or paricalcitol. The control group underwent a sham surgery. The treatment was done for 15 days (30 ng/kg). The following were determined: biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; VDR, AT(1) receptor, and NADPH oxidase 4 expression; and NADPH oxidase activity (in total and in mitochondrial fractions from the renal cortex). VDR activation prevented fibrosis (20 ± 5 vs. 60 ± 10%) and the number of TUNEL-positive apoptotic cells (10 ± 3 vs. 25 ± 4) in UUO. Biochemical, histological, and molecular studies suggest mitochondrial injury. Electron microscopy revealed in UUO electronically luminous material in the nucleus. Some mitochondria were increased in size and contained dilated crests and larger than normal spaces in their interiors. These changes were not present with paricalcitol treatment. Additionally, high AT(1)-receptor mRNA and NADPH activity was reverted in mitochondrial fractions from obstructed paricalcitol-treated animals (0.58 ± 0.06 vs. 0.95 ± 0.05 relative densitometry units and 9,000 ± 800 vs. 15,000 ± 1,000 relative fluorescence units·μg protein(-1)·min(-1), respectively). These changes were consistent with an improvement in VDR expression (0.75 ± 0.05 vs. 0.35 ± 0.04 relative densitometry units). These results suggest that paricalcitol confers a protective effect and reveal, as well, a possible AT(1) receptor-dependent protective effect that occurs at the mitochondrial level.
Fil: García, Isabel Mercedes. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Altamirano, Berta Liliana. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Fornes, Miguel Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Molina, Marisa Nile. Universidad "Juan Agustín Maza". Facultad de Farmacia y Bioquímica; Argentina
Fil: Ferder, León. Ponce School Of Medicine; Puerto Rico
Fil: Manucha, Walter Ariel Fernando. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
description Vitamin D slows the progression of chronic kidney disease. Furthermore, activators of vitamin D receptors (VDR) have suppressant effects on the renin-angiotensin system, as well as anti-inflammatory and antifibrotic actions. This study aimed to evaluate the cytoprotective effects of paricalcitol, a VDR activator, at the mitochondrial level using an obstructive nephropathy model [unilateral ureteral obstruction (UUO)]. Rats subjected to UUO and controls were treated daily with vehicle or paricalcitol. The control group underwent a sham surgery. The treatment was done for 15 days (30 ng/kg). The following were determined: biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; VDR, AT(1) receptor, and NADPH oxidase 4 expression; and NADPH oxidase activity (in total and in mitochondrial fractions from the renal cortex). VDR activation prevented fibrosis (20 ± 5 vs. 60 ± 10%) and the number of TUNEL-positive apoptotic cells (10 ± 3 vs. 25 ± 4) in UUO. Biochemical, histological, and molecular studies suggest mitochondrial injury. Electron microscopy revealed in UUO electronically luminous material in the nucleus. Some mitochondria were increased in size and contained dilated crests and larger than normal spaces in their interiors. These changes were not present with paricalcitol treatment. Additionally, high AT(1)-receptor mRNA and NADPH activity was reverted in mitochondrial fractions from obstructed paricalcitol-treated animals (0.58 ± 0.06 vs. 0.95 ± 0.05 relative densitometry units and 9,000 ± 800 vs. 15,000 ± 1,000 relative fluorescence units·μg protein(-1)·min(-1), respectively). These changes were consistent with an improvement in VDR expression (0.75 ± 0.05 vs. 0.35 ± 0.04 relative densitometry units). These results suggest that paricalcitol confers a protective effect and reveal, as well, a possible AT(1) receptor-dependent protective effect that occurs at the mitochondrial level.
publishDate 2012
dc.date.none.fl_str_mv 2012-04-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/81956
García, Isabel Mercedes; Altamirano, Berta Liliana; Mazzei, Luciana Jorgelina; Fornes, Miguel Walter; Molina, Marisa Nile; et al.; Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy; American Physiological Society; American Journal Of Physiology-renal Physiology; 302; 12; 4-4-2012; 1565-1605
1931-857X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/81956
identifier_str_mv García, Isabel Mercedes; Altamirano, Berta Liliana; Mazzei, Luciana Jorgelina; Fornes, Miguel Walter; Molina, Marisa Nile; et al.; Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy; American Physiological Society; American Journal Of Physiology-renal Physiology; 302; 12; 4-4-2012; 1565-1605
1931-857X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1152/ajprenal.00617.2011
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/ajprenal.00617.2011
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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