Induction of apoptosis by human amylin in RINm5F islet beta-cells is associated with enhanced expression of p53 and p21WAF1/CIP1.
Human amylin (10 microM) significantly inhibited RINm5F islet beta-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 beta-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 beta-cells with different proliferation rates respond differently to human amylin, and that human amylin may be more toxic to proliferating cells.
Zhang
S
S
The School of Biological Sciences, University of Auckland, New Zealand.
Liu
J
J
Saafi
E L
EL
Cooper
G J
GJ
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D053938:DNA Fragmentation / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects*; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D051381:Rats
D000682:Amyloid; C493956:CDKN1A protein, human; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D058228:Islet Amyloid Polypeptide