P2Z purinoreceptor ligation induces activation of caspases with distinct roles in apoptotic and necrotic alterations of cell death

FEBS Letters

Bauer, Manuel K.A.¹  Schulze-Osthoff, Klaus¹  Wesselborg, Sebastian¹  Los, Marek¹  Vandenabeele, Peter²  Ferrari, Davide¹ 

[1] Department of Internal Medicine I, Medical Clinics, Eberhard-Karls-University, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany;Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, Ghent, Belgium

关键词: Apoptosis;    ATP;    Caspase;    Necrosis;    P2Z;    Purinoreceptor;    BrdU;    5′-bromo-2′-deoxyuridine;    DEVD;    N-acetyl-Asp-Glu-Val-Asp-aldehyde;    LDH;    lactate dehydrogenase;    PARP;    poly(ADP-ribose) polymerase;    YVAD;    N-acetyl-Tyr-Val-Ala-Asp-chloromethylketone;    zVAD;    benzyloxycarbonyl-Val-Ala-Asp(OMe)fluoro-methylketone;   

DOI  :  10.1016/S0014-5793(99)00270-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Myeloic cells express a peculiar surface receptor for extracellular ATP, called the P2Z/P2X₇ purinoreceptor, which is involved in cell death signalling. Here, we investigated the role of caspases, a family of proteases implicated in apoptosis and the cytokine secretion. We observed that extracellular ATP induced the activation of multiple caspases including caspase-1, -3 and -8, and subsequent cleavage of the caspase substrates PARP and lamin B. Using caspase inhibitors, it was found that caspases were specifically involved in ATP-induced apoptotic damage such as chromatin condensation and DNA fragmentation. In contrast, inhibition of caspases only marginally affected necrotic alterations and cell death proceeded normally whether or not nuclear damage was blocked. Our results therefore suggest that the activation of caspases by the P2Z receptor is required for apoptotic but not necrotic alterations of ATP-induced cell death.

【 授权许可】

Unknown