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

• Published in: FEBS letters Vol. 455; no. 3; pp. 315 - 320
• Main Authors: Zhang, Shaoping, Liu, Junxi, Saafi, ‘Etuate L., Cooper, Garth J.S.
• Format: Journal Article
• Language: English
• Published: England 23-07-1999
• Subjects: Amyloid - pharmacology; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Base Sequence; Cell Division - drug effects; Cell Line; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - genetics; DNA Fragmentation - drug effects; DNA Primers - genetics; Gene Expression - drug effects; Genes, p53 - drug effects; Human amylin; Humans; Islet Amyloid Polypeptide; Islet β-cell; Islets of Langerhans - cytology; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Microscopy, Electron, Scanning; p21WAF1/CIP1; p53; Rats
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)00894-7

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 p21WAF/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.