Differentiation potentiates oxidant injury to mitochondria by hydrogen peroxide in Friend's erythroleukemia cells

FEBS Letters

Lippe, Giovanna¹  Comelli, Marina¹  Mavelli, Irene¹ 

[1] Department of Biomedical Sciences and Technologies, University of Udine, Via Gervasutta 48, 33100 Udine, Italy

关键词: Hydrogen peroxide;    Oxidative phosphorylation;    Heme;    Iron;    F0F1 ATPsynthase;    Friend's erythroleukemia cells;    FELC;    Friend's erythroleukemia cells;    HMBA;    N;    N′-hexametylene bisacetamide;    PBS;    phospate-buffered saline;    HEPES;    N-(2-hydroxyethyl) piperazine-N′-(2-ethanesulfonic acid);    EGTA;    ethylene glycol-bis (β-aminoethyl ether) N;    N;    N;    N′-tetraacetic acid;    RCR;    respiratory control ratio;    FCCP;    carbonyl cyanide p-trifluromethoxyphenyl hydrazone;    BHT;    butylated hydroxytoluene;    DMSO;    dimethyl sulfoxide;    DFO;    desferrioxamine methanesulphonate;    FO;    ferrioxamine;   

DOI  :  10.1016/0014-5793(94)00882-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Oxidative damage to mitochondrial functions was investigated upon non-lethal treatment with H₂O₂ of Friend's erythroleukemia cells induced to differentiate, in comparison with the parental cell line. Both respiration and maximal ATP synthase capacity were more severely diminished by H₂O₂ in induced cells. The effects were mediated by intracellular redox-active iron and OH^. radicals. Specifically, the mechanisms of the selective oxidant injury to F₀F₁ ATP synthase observed in differentiating cells likely involved impairment of F₀—F₁ coupling sensitive to oligomycin. We suggest a Fenton-like reaction of H₂O₂ with iron ions, more available in the differentiating cells, as occurring at the surface and/or in the lipid bulk phase of the inner mitochondrial membrane, thus injuring subunits responsible for the coupling of F₀F₁ ATP synthase through generation in situ of the actual damaging species. Besides, we propose heme iron as the most likely candidate for such reaction in induced cells actively synthesizing heme. In accordance, pretreatment of uninduced cells with hemin made H₂O₂-damage qualitatively identical.

【 授权许可】

Unknown