Increasing evidence suggests that angiotensin II may act as a growth factor for several muscle cell types. Angiotensin II stimulation activates many immediate early response genes like c-Fos, c-Jun, c-Myc and Egr-1 in both vascular smooth muscle cells and cardiomyocytes, independently of whether a hyperplastic or hypertrophic response is taking place. In this study we report that angiotensin II significantly stimulates AP1-driven transcription in mouse skeletal muscle cells C2C12 stably transfected with a TRE-tk-CAT plasmid in a dose-dependent manner (peak stimulation at 10-5 M of angiotensin II). Moreover, angiotensin II increases the binding of the AP1 complex to its DNA target in both quiescent C2C12 myoblasts and in differentiated C2C12 myotubes. Most of the TRE-bound complexes in both unstimulated and angiotensin II-treated cells consist of c-jun/c-fos heterodimers. Using a set of different protein kinase inhibitors, including HA1004, H7, tyrphostin, genistein and staurosporine, we could demonstrate that the angiotensin II-induced AP1 binding increase is not mediated by the cAMP-dependent pathway and that protein kinase C and tyrosine kinases are involved. Treatment of C2C12 cells with H2O2 induces a dose-dependent increase in c-jun/c-fos heterodimer binding, specifically reverted by the cysteine derivative and glutathione precursor N-acetyl-L-cysteine (NAC). The observation that the induction by angiotensin II of both the AP1 DNA binding activity and DNA synthesis in quiescent C2C12 myoblasts is abolished by NAC strongly suggests a role for reactive oxygen intermediates (ROIs) in the intracellular transduction of angiotensin II signals for immediate early gene induction and for cell proliferation.

REACTIVE OXYGEN INTERMEDIATES (ROIS) ARE INVOLVED IN THE INTRACELLULAR TRANSDUCTION OF ANGIOTENSIN-II SIGNAL IN C2C12 CELLS / Pier Lorenzo, Puri; M. L., Avantaggiati; Vito Lelio, Burgio; Paolo, Chirillo; Daniela, Collepardo; Gioacchino, Natoli; Clara, Balsano; Levrero, Massimo. - In: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. - ISSN 0077-8923. - 752:1 Cardiac Growt(1995), pp. 394-405. (Intervento presentato al convegno NATO Advanced Research Workshop on Cardiac Growth and Regeneration tenutosi a VITERBO, ITALY nel JUN 19-24, 1994) [10.1111/j.1749-6632.1995.tb17447.x].

REACTIVE OXYGEN INTERMEDIATES (ROIS) ARE INVOLVED IN THE INTRACELLULAR TRANSDUCTION OF ANGIOTENSIN-II SIGNAL IN C2C12 CELLS

LEVRERO, Massimo
1995

Abstract

Increasing evidence suggests that angiotensin II may act as a growth factor for several muscle cell types. Angiotensin II stimulation activates many immediate early response genes like c-Fos, c-Jun, c-Myc and Egr-1 in both vascular smooth muscle cells and cardiomyocytes, independently of whether a hyperplastic or hypertrophic response is taking place. In this study we report that angiotensin II significantly stimulates AP1-driven transcription in mouse skeletal muscle cells C2C12 stably transfected with a TRE-tk-CAT plasmid in a dose-dependent manner (peak stimulation at 10-5 M of angiotensin II). Moreover, angiotensin II increases the binding of the AP1 complex to its DNA target in both quiescent C2C12 myoblasts and in differentiated C2C12 myotubes. Most of the TRE-bound complexes in both unstimulated and angiotensin II-treated cells consist of c-jun/c-fos heterodimers. Using a set of different protein kinase inhibitors, including HA1004, H7, tyrphostin, genistein and staurosporine, we could demonstrate that the angiotensin II-induced AP1 binding increase is not mediated by the cAMP-dependent pathway and that protein kinase C and tyrosine kinases are involved. Treatment of C2C12 cells with H2O2 induces a dose-dependent increase in c-jun/c-fos heterodimer binding, specifically reverted by the cysteine derivative and glutathione precursor N-acetyl-L-cysteine (NAC). The observation that the induction by angiotensin II of both the AP1 DNA binding activity and DNA synthesis in quiescent C2C12 myoblasts is abolished by NAC strongly suggests a role for reactive oxygen intermediates (ROIs) in the intracellular transduction of angiotensin II signals for immediate early gene induction and for cell proliferation.
1995
01 Pubblicazione su rivista::01a Articolo in rivista
REACTIVE OXYGEN INTERMEDIATES (ROIS) ARE INVOLVED IN THE INTRACELLULAR TRANSDUCTION OF ANGIOTENSIN-II SIGNAL IN C2C12 CELLS / Pier Lorenzo, Puri; M. L., Avantaggiati; Vito Lelio, Burgio; Paolo, Chirillo; Daniela, Collepardo; Gioacchino, Natoli; Clara, Balsano; Levrero, Massimo. - In: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. - ISSN 0077-8923. - 752:1 Cardiac Growt(1995), pp. 394-405. (Intervento presentato al convegno NATO Advanced Research Workshop on Cardiac Growth and Regeneration tenutosi a VITERBO, ITALY nel JUN 19-24, 1994) [10.1111/j.1749-6632.1995.tb17447.x].
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/438572
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 16
social impact