Cholesterol oxidation products are increasingly considered as much more bioactive than the parent compound in the mutifactored and multistep process which characterizes atherosclerosis. In particular, 7-ketocholesterol has been reported to induce oxidative stress as well as a marked pro-apoptotic effect in vascular cells including macrophages. With the aim to investigate a possible pathogenic correlation between the two events, cultivated murine macrophages were challenged with a concentration of 7-ketocholesterol actually detectable in human vasculature. Conclusive proof was obtained of a primary role of NADPH-oxidase in the overproduction of reactive oxygen species within cells treated with the oxysterol. In addition, such oxidative burst occurred very early after cell intoxication and it was definitely demonstrated as able to lead cells to apoptotic death. In fact, two metabolic inhibitors of NADPH-oxidase and the antioxidant epicatechin very well counteracted 7-ketocholesterol-induced apoptosis by preventing the oxysterol pro-oxidant action.

Early involvement of ROS overproduction in apoptosis induced by 7-ketocholesterol.

LEONARDUZZI, Gabriella Marisa;VIZIO, Barbara;SOTTERO, Barbara;GAMBA, Paola Francesca;MASCIA, Cinzia;CHIARPOTTO, Elena Maria;POLI, Giuseppe;BIASI, Fiorella
2006

Abstract

Cholesterol oxidation products are increasingly considered as much more bioactive than the parent compound in the mutifactored and multistep process which characterizes atherosclerosis. In particular, 7-ketocholesterol has been reported to induce oxidative stress as well as a marked pro-apoptotic effect in vascular cells including macrophages. With the aim to investigate a possible pathogenic correlation between the two events, cultivated murine macrophages were challenged with a concentration of 7-ketocholesterol actually detectable in human vasculature. Conclusive proof was obtained of a primary role of NADPH-oxidase in the overproduction of reactive oxygen species within cells treated with the oxysterol. In addition, such oxidative burst occurred very early after cell intoxication and it was definitely demonstrated as able to lead cells to apoptotic death. In fact, two metabolic inhibitors of NADPH-oxidase and the antioxidant epicatechin very well counteracted 7-ketocholesterol-induced apoptosis by preventing the oxysterol pro-oxidant action.
8
375
380
Leonarduzzi G; Vizio B; Sottero B; Verde V; Gamba P; Mascia C; Chiarpotto E; Poli G; Biasi F
File in questo prodotto:
File Dimensione Formato  
ARS 2006.pdf

Accesso riservato

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 380.68 kB
Formato Adobe PDF
380.68 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

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: http://hdl.handle.net/2318/101678
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 58
  • ???jsp.display-item.citation.isi??? 60
social impact