Phospholipase C/Protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor

Raul Vivar, Cristian Soto, Miguel Copaja, Francisca Mateluna, Pablo Aranguiz, Juan Pablo Muñoz, Mario Chiong, Lorena Garcia, Alan Letelier, Walter G. Thomas, Sergio Lavandero, Guillermo Díaz-Araya

Resultado de la investigación: Article

23 Citas (Scopus)

Resumen

Cardiac fibroblasts are the major non-myocyte cell constituent in the myocardium, and they are involved in heart remodeling. Angiotensin II type 1 receptor (AT1R) mediates the established actions of angiotensin II (Ang II), and changes in its expression have been reported in cardiac fibroblasts after myocardial infarction. However, the AT1R-dependent signaling pathways involved in cardiac fibroblast death remain unknown. Using adenovirus, we ectopically expressed AT1R in cultured neonatal rat cardiac fibroblasts and investigated the role of the phospholipase (PLC)/protein kinase C (PKC) pathway on Ang II-dependent death. Ang II induced cardiac fibroblast death characterized by an early loss of mitochondrial membrane potential, increased Bax/Bcl-2 ratio, caspase-3 activation, and DNA fragmentation. All these effects were prevented by the AT1R antagonist losartan, PLC inhibitor U73122, and PKC inhibitor Gö6976. We conclude that Ang II stimulates the intrinsic apoptotic pathway in cultured cardiac fibroblasts by the AT1R/PLC/PKC signaling pathway.

Idioma originalEnglish
Páginas (desde-hasta)184-190
Número de páginas7
PublicaciónJournal of Cardiovascular Pharmacology
Volumen52
N.º2
DOI
EstadoPublished - 1 ago 2008

Huella dactilar

Type C Phospholipases
Angiotensin II
Protein Kinase C
Angiotensin Type 1 Receptor
Fibroblasts
Apoptosis
Angiotensin II Type 1 Receptor Blockers
Losartan
Phospholipases
Protein C Inhibitor
Mitochondrial Membrane Potential
DNA Fragmentation
Protein Kinase Inhibitors
Adenoviridae
Caspase 3
Myocardium
Myocardial Infarction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Citar esto

Vivar, Raul ; Soto, Cristian ; Copaja, Miguel ; Mateluna, Francisca ; Aranguiz, Pablo ; Muñoz, Juan Pablo ; Chiong, Mario ; Garcia, Lorena ; Letelier, Alan ; Thomas, Walter G. ; Lavandero, Sergio ; Díaz-Araya, Guillermo. / Phospholipase C/Protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor. En: Journal of Cardiovascular Pharmacology. 2008 ; Vol. 52, N.º 2. pp. 184-190.
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title = "Phospholipase C/Protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor",
abstract = "Cardiac fibroblasts are the major non-myocyte cell constituent in the myocardium, and they are involved in heart remodeling. Angiotensin II type 1 receptor (AT1R) mediates the established actions of angiotensin II (Ang II), and changes in its expression have been reported in cardiac fibroblasts after myocardial infarction. However, the AT1R-dependent signaling pathways involved in cardiac fibroblast death remain unknown. Using adenovirus, we ectopically expressed AT1R in cultured neonatal rat cardiac fibroblasts and investigated the role of the phospholipase (PLC)/protein kinase C (PKC) pathway on Ang II-dependent death. Ang II induced cardiac fibroblast death characterized by an early loss of mitochondrial membrane potential, increased Bax/Bcl-2 ratio, caspase-3 activation, and DNA fragmentation. All these effects were prevented by the AT1R antagonist losartan, PLC inhibitor U73122, and PKC inhibitor G{\"o}6976. We conclude that Ang II stimulates the intrinsic apoptotic pathway in cultured cardiac fibroblasts by the AT1R/PLC/PKC signaling pathway.",
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author = "Raul Vivar and Cristian Soto and Miguel Copaja and Francisca Mateluna and Pablo Aranguiz and Mu{\~n}oz, {Juan Pablo} and Mario Chiong and Lorena Garcia and Alan Letelier and Thomas, {Walter G.} and Sergio Lavandero and Guillermo D{\'i}az-Araya",
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Vivar, R, Soto, C, Copaja, M, Mateluna, F, Aranguiz, P, Muñoz, JP, Chiong, M, Garcia, L, Letelier, A, Thomas, WG, Lavandero, S & Díaz-Araya, G 2008, 'Phospholipase C/Protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor', Journal of Cardiovascular Pharmacology, vol. 52, n.º 2, pp. 184-190. https://doi.org/10.1097/FJC.0b013e318181fadd

Phospholipase C/Protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor. / Vivar, Raul; Soto, Cristian; Copaja, Miguel; Mateluna, Francisca; Aranguiz, Pablo; Muñoz, Juan Pablo; Chiong, Mario; Garcia, Lorena; Letelier, Alan; Thomas, Walter G.; Lavandero, Sergio; Díaz-Araya, Guillermo.

En: Journal of Cardiovascular Pharmacology, Vol. 52, N.º 2, 01.08.2008, p. 184-190.

Resultado de la investigación: Article

TY - JOUR

T1 - Phospholipase C/Protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor

AU - Vivar, Raul

AU - Soto, Cristian

AU - Copaja, Miguel

AU - Mateluna, Francisca

AU - Aranguiz, Pablo

AU - Muñoz, Juan Pablo

AU - Chiong, Mario

AU - Garcia, Lorena

AU - Letelier, Alan

AU - Thomas, Walter G.

AU - Lavandero, Sergio

AU - Díaz-Araya, Guillermo

PY - 2008/8/1

Y1 - 2008/8/1

N2 - Cardiac fibroblasts are the major non-myocyte cell constituent in the myocardium, and they are involved in heart remodeling. Angiotensin II type 1 receptor (AT1R) mediates the established actions of angiotensin II (Ang II), and changes in its expression have been reported in cardiac fibroblasts after myocardial infarction. However, the AT1R-dependent signaling pathways involved in cardiac fibroblast death remain unknown. Using adenovirus, we ectopically expressed AT1R in cultured neonatal rat cardiac fibroblasts and investigated the role of the phospholipase (PLC)/protein kinase C (PKC) pathway on Ang II-dependent death. Ang II induced cardiac fibroblast death characterized by an early loss of mitochondrial membrane potential, increased Bax/Bcl-2 ratio, caspase-3 activation, and DNA fragmentation. All these effects were prevented by the AT1R antagonist losartan, PLC inhibitor U73122, and PKC inhibitor Gö6976. We conclude that Ang II stimulates the intrinsic apoptotic pathway in cultured cardiac fibroblasts by the AT1R/PLC/PKC signaling pathway.

AB - Cardiac fibroblasts are the major non-myocyte cell constituent in the myocardium, and they are involved in heart remodeling. Angiotensin II type 1 receptor (AT1R) mediates the established actions of angiotensin II (Ang II), and changes in its expression have been reported in cardiac fibroblasts after myocardial infarction. However, the AT1R-dependent signaling pathways involved in cardiac fibroblast death remain unknown. Using adenovirus, we ectopically expressed AT1R in cultured neonatal rat cardiac fibroblasts and investigated the role of the phospholipase (PLC)/protein kinase C (PKC) pathway on Ang II-dependent death. Ang II induced cardiac fibroblast death characterized by an early loss of mitochondrial membrane potential, increased Bax/Bcl-2 ratio, caspase-3 activation, and DNA fragmentation. All these effects were prevented by the AT1R antagonist losartan, PLC inhibitor U73122, and PKC inhibitor Gö6976. We conclude that Ang II stimulates the intrinsic apoptotic pathway in cultured cardiac fibroblasts by the AT1R/PLC/PKC signaling pathway.

KW - Angiotensin II

KW - Apoptosis

KW - AT receptor

KW - Cell death

KW - Fibroblast

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JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

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