Arachidonic acid induces calcium-dependent mitochondrial formation of species promoting strand scission of genomic DNA.
Free Radic Biol Med
; 28(11): 1619-27, 2000 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-10938458
ABSTRACT
Both the phospholipase A(2) activator melittin and reagent arachidonic acid (AA) are poor inducers of DNA single strand breaks in U937 cells. These responses, however, were dramatically increased by the calcium-mobilizing agent caffeine (Cf) or by the respiratory substrate pyruvate via a mechanism that involved enforced mitochondrial Ca(2+) accumulation and that was sensitive to lipoxygenase inhibitors. In permeabilized cells, the DNA damage generated by AA in combination with either Cf, L-malate or CaCl(2) was blunted by catalase. AA generated DNA strand scission also in HeLa cells supplemented with pyruvate via a mechanism identical to that observed in U937 cells. This response was associated with an enforced formation of free radical species. These results demonstrate that mitochondria play a pivotal role in the DNA-damaging response evoked by AA and provide the bases for a calcium-dependent mechanism whereby the AA produced during inflammatory processes may affect various pathologic conditions, including carcinogenesis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Cálcio
/
Ácido Araquidônico
/
Mitocôndrias
Limite:
Humans
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article