Mitochondrial DNA damage associated with lipid peroxidation of the mitochondrial membrane induced by Fe2+-citrate

Anais da Academia Brasileira de Ciências

Andréa M. Almeida²  Clélia R.a. Bertoncini¹  Jiri Borecký²  Nadja C. Souza-pinto²  Aníbal E. Vercesi² 

[1] ,Universidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de Patologia ClínicaCampinas SP ,Brasil

关键词: iron;    lipid peroxidation;    mitochondria;    mtDNA;    oxidative stress;    ferro;    peroxidação lipídica;    mitocôndrias;    DNAmt;    estresse oxidativo;   

DOI  :  10.1590/S0001-37652006000300010

来源: SciELO

【 摘 要 】

Iron imbalance/accumulation has been implicated in oxidative injury associated with many degenerative diseases such as hereditary hemochromatosis, beta-thalassemia, and Friedreich's ataxia. Mitochondria are particularly sensitive to iron-induced oxidative stress - high loads of iron cause extensive lipid peroxidation and membrane permeabilization in isolated mitochondria. Here we detected and characterized mitochondrial DNA damage in isolated rat liver mitochondria exposed to a Fe2+-citrate complex, a small molecular weight complex. Intense DNA fragmentation was induced after the incubation of mitochondria with the iron complex. The detection of 3' phosphoglycolate ends at the mtDNA strand breaks by a 32P-postlabeling assay, suggested the involvement of hydroxyl radical in the DNA fragmentation induced by Fe2+-citrate. Increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine also suggested that Fe2+-citrate-induced oxidative stress causes mitochondrial DNA damage. In conclusion, our results show that iron-mediated lipid peroxidation was associated with intense mtDNA damage derived from the direct attack of reactive oxygen species.

【 授权许可】

CC BY   
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