Induction of apoptosis by human amylin in RINm5F islet β‐cells is associated with enhanced expression of p53 and p21WAF1/CIP1

FEBS Letters

Saafi, ‘Etuate L.¹  Liu, Junxi¹  Cooper, Garth J.S.¹  Zhang, Shaoping¹ 

[1] The School of Biological Sciences, Level 4, University of Auckland, Auckland, New Zealand

关键词: Human amylin;    Islet β-cell;    Apoptosis;    p53;    p21WAF1/CIP1;   

DOI  :  10.1016/S0014-5793(99)00894-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Human amylin (10 μM) significantly inhibited RINm5F islet β-cell proliferation and evoked apoptosis associated with typical degenerative ultrastructural changes and DNA fragmentation, whereas rat amylin did not. Time course analysis showed that human amylin elicited apoptosis in a passage-dependent manner. Expression of the apoptosis-related genes p53, bcl-2 and WAF1/CIP1 was examined using Northern blots. mRNAs corresponding to p53 and to p21^WAF/CIP1 were remarkably increased following human amylin treatment, whereas no change in bcl-2 was detected. Our data suggest a role of p53 and p21 in human amylin-induced β-cell apoptosis. Furthermore, cells with higher proliferative potential (lower passage) were found to be more susceptible to apoptosis and to induction of p53, suggesting that β-cells with different proliferation rates respond differently to human amylin, and that human amylin may be more toxic to proliferating cells.

【 授权许可】

Unknown