Annexin A1 processing is associated with caspase‐dependent apoptosis in BZR cells

FEBS Letters

Duca, L.³  Antonicelli, F.³  El Btaouri, H.³  Rahman, I.¹  Sallenave, J.M.⁴  Radke, S.²  Haye, B.³  Debret, R.³ 

[1] COLT, Medical School, The University of Edinburgh, Edinburgh, UK;ICGM, INSERM U 332, Paris, France;Laboratoire de Biochimie, CNRS FRE 2534, Université de Reims Champagne-Ardenne, UFR Sciences, Moulin de la Housse, P.O. Box 1039, 51687 Reims Cedex 2, France;Rayne Laboratories, Medical School, The University of Edinburgh, Edinburgh, UK

关键词: Annexin AI;    Ceramide;    Apoptosis;    Caspase;    BZR cell;   

DOI  :  10.1016/S0014-5793(03)00570-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Annexins are widely distributed and have been described in lung as well as in other cells and tissues. Annexin I (ANX AI) is a member of the calcium-dependent phospholipid binding protein family. Besides its anti-inflammatory function, ANX AI has been involved in several mechanisms such as the Erk repression pathway or apoptosis. To investigate the role of ANX AI on apoptosis in broncho-alveolar cells, we have constructed a plasmid containing the ANX AI full length cDNA. Transfected BZR cells displayed a higher level of both forms of ANX AI (37 and 33 kDa) as well as a decrease in cell viability (two-fold versus cells transfected with an empty vector). In order to analyse the endogenous ANX AI processing during stimulus-induced apoptosis, BZR cells were treated with a commonly used inducer, i.e. C2 ceramides. In these conditions, microscopic analysis revealed chromatin condensation in dying cells and the Bcl-2, Bcl-x_L/Bax mRNA balance was altered. Caspase-3 is one of the key executioners of apoptosis, being responsible for the cleavage of many proteins such as the nuclear enzyme poly(ADP-ribose) polymerase (PARP). We demonstrate that caspase-3 was activated after 4 h treatment in the presence of ceramide leading to the cleavage of PARP. Dose–response experiments revealed that cell morphology and viability modifications following ceramide treatment were accompanied by an increase in endogenous ANX AI processing. Interestingly, in both ceramide and transfection experiments, the ANX AI cleaved form was enhanced whereas pre-treatment with the caspase inhibitor Z-VAD-fmk abolished ANX AI cleavage. In conclusion, this study demonstrates a complex regulatory role of caspase-dependent apoptosis where ANX AI is processed at the N-terminal region which could give susceptibility to apoptosis upon ceramide treatment.

【 授权许可】

Unknown