Over‐expression of Bcl‐2 does not protect cells from hypericin photo‐induced mitochondrial membrane depolarization, but delays subsequent events in the apoptotic pathway

FEBS Letters

Israël, Nicole³  Sureau, Franck¹  Chaloupka, Roman¹  Petit, Patrice Xavier² 

[1] Laboratoire de Physicochimie Biomoléculaire et Cellulaire (CNRS ESA 7033), Université P. et M. Curie, Case 138, 4 Place Jussieu, F-75252 Paris Cedex 05, France;Unité de Recherche en Physiologie et Pathologie Génétiques et Moléculaires (INSERM U129), I.C.G.M., Faculté de médecine Cochin, Port Royal, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France;Unité de Biologie des Rétrovirus, Institut Pasteur, 28 rue du docteur Roux, 75724 Paris Cedex 15, France

关键词: Apoptosis;    Bcl-2;    Caspase;    Cellular photosensitization;    Cyclosporin A;    Hypericin;    Mitochondrial membrane potential;    HY;    hypericin;    Δψ m;    mitochondrial membrane potential;    PS;    phosphatidylserine;    CsA;    cyclosporin A;    DiOC6(3);    3;    3′-dihexyloxacarbocyanine iodide;    BCECF-AM;    2′;    7′-bis(2-carboxyethyl)-5-(and 6)-carboxyfluorescein acetoxymethylester;    FITC;    fluorescein isothiocyanate;    PI;    propidium iodide;    MPT;    mitochondrial permeability transition;    BA;    bongkrekic acid;   

DOI  :  10.1016/S0014-5793(99)01538-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Hypericin (HY) is a powerful photo-inducer of apoptosis in Jurkat cells as measured by caspase-3 activation, cell shrinkage, phosphatidylserine (PS) exposure and the appearance of hypoploid DNA. These processes are preceded by rapid Bcl-2-independent mitochondrial transmembrane depolarization and a drop in cytoplasmic pH. Pre-incubation of cells with inhibitors of the mitochondrial permeability transition pore, such as cyclosporin A or bongkrekic acid, does not protect cells from mitochondrial membrane potential (Δψ _m) decrease. However, monitoring of mitochondrial entrapped calcein by confocal fluorescence imaging gives clear evidence of HY photo-induced mitochondrial permeability. This should be considered as the result of a non-specific alteration of mitochondrial membrane integrity brought about by lipid peroxidation. Nevertheless, synthesis of the anti-apoptotic protein Bcl-2 appears to delay the subsequent time course of PS exposure and to reduce caspase-3 activation and the fraction of cells which become hypoploid. We interpret this partially protective effect as the consequence of a direct interaction of Bcl-2 with cytosolic cytochrome c previously released from mitochondria upon Δψ _m decrease and/or of Bcl-2 inhibition of the deleterious retro-effect of caspase-3 on the mitochondrial permeability transition pore and/or the mitochondrial membrane components.

【 授权许可】

Unknown