期刊论文详细信息
FEBS Letters
Fas‐triggered phosphatidylserine exposure is modulated by intracellular ATP
Fadeel, Bengt1  Gleiss, Bettina1  Gogvadze, Vladimir1  Orrenius, Sten1 
[1] Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, SE-171 77 Stockholm, Sweden
关键词: Aminophospholipid translocase;    Apoptosis;    Adenosine triphosphate;    Phosphatidylserine;    Phospholipid scramblase;    ATP;    adenosine triphosphate;    DEVD-AMC;    Asp-Glu-Val-Asp-7-amino-4-methylcoumarin;    2-DG;    2-deoxyglucose;    GAPDH;    glyceraldehyde-3-phosphate dehydrogenase;    IFN;    interferon;    NBD;    1-oleoyl-2-[6-[(7-nitro-2-1;    3-benzoxadiazol-4-yl) amino]caproyl]-sn-glycero-3;    NEM;    N-ethylmaleimide;    PLS;    phospholipid scramblase;    PS;    phosphatidylserine;    zVAD-fmk;    benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone;   
DOI  :  10.1016/S0014-5793(02)02743-6
学科分类:生物化学/生物物理
来源: John Wiley & Sons Ltd.
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【 摘 要 】

Recognition signals are displayed on the cell surface during apoptosis that enable macrophages to engulf and dispose of the dying cell. A common signal is the externalization of phosphatidylserine (PS). Studies in erythrocytes and platelets have suggested that PS exposure requires the concomitant activation of a phospholipid scramblase (PLS) and inhibition of an adenosine triphosphate (ATP)-dependent aminophospholipid translocase. However, the molecular mechanism underlying PS exposure during apoptosis remains poorly understood. In this study, we provide evidence that expression of PLS is neither necessary nor sufficient for PS exposure during Fas-triggered apoptosis. On the other hand, egress of PS is shown to correlate with a decline in intracellular ATP and inhibition of aminophospholipid translocase activity upon Fas stimulation. Moreover, suppression of intracellular ATP levels by the glucose anti-metabolite, 2-deoxyglucose, alone or in combination with glucose-free medium, potentiates Fas-induced PS exposure in the PLS-expressing Jurkat cell line and enables PLS-defective Raji cells to externalize PS in response to Fas ligation. These studies suggest that intracellular ATP levels can modulate the externalization of PS during apoptosis, and implicate the ATP-dependent aminophospholipid translocase in this process.

【 授权许可】

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