In this paper we present experimental evidence indicating that DNA cleavage induced by tert-butylhydroperoxide in U937 cells can be enhanced via ATP-mediated activation of membrane receptors coupled with hydrolysis of phosphatidylinositol 4,5-bisphosphate. The mechanism whereby ATP exerts this effect involves release of Ca2+ from the inositol 1,4,5-trisphosphate (IP3)-sensitive stores, further release of the cation from the ryanodine receptor, mitochondrial clearance of the fraction of Ca2+ derived from the ryanodine receptor, and Ca2+-dependent mitochondrial formation of DNA-damaging species. IP3-generating agonists must therefore be considered as potential modulators of the genotoxic effects of tert-butylhydroperoxide.

The inositol 1,4,5-trisphosphate-generating agonist ATP enhances DNA cleavage induced by tert-butylhydroperoxide.

GUIDARELLI, ANDREA;CANTONI, ORAZIO
1998-01-01

Abstract

In this paper we present experimental evidence indicating that DNA cleavage induced by tert-butylhydroperoxide in U937 cells can be enhanced via ATP-mediated activation of membrane receptors coupled with hydrolysis of phosphatidylinositol 4,5-bisphosphate. The mechanism whereby ATP exerts this effect involves release of Ca2+ from the inositol 1,4,5-trisphosphate (IP3)-sensitive stores, further release of the cation from the ryanodine receptor, mitochondrial clearance of the fraction of Ca2+ derived from the ryanodine receptor, and Ca2+-dependent mitochondrial formation of DNA-damaging species. IP3-generating agonists must therefore be considered as potential modulators of the genotoxic effects of tert-butylhydroperoxide.
File in 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/11576/1882168
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 12
social impact