کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2554788 | 1124989 | 2006 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Sequential activation of caspases and synergistic β-cell cytotoxicity by palmitate and anti-Fas antibodies Sequential activation of caspases and synergistic β-cell cytotoxicity by palmitate and anti-Fas antibodies](/preview/png/2554788.png)
To assess the mechanism of β-cell lipotoxicity in comparison with Fas-mediated cell death, we used a mouse β-cell clone stably transfected with human Fas. Palmitate induced β-cell death in correlation with medium glucose levels between 5 and 20 mmol/l, while Fas-mediated cytotoxicity was observed irrespective of glucose concentration. At the glucose level of 10 mmol/l, palmitate induced caspase-6 activity within 3 h, and caspase-3 activity after a lag period of 6 h. The activities of caspases were correlated with glucose concentration. A caspase-6 inhibitor attenuated caspase-3 activation and cell death induced by palmitate. Oxfenicine, an inhibitor of carnitine palmitoyltransferase-1, attenuated both palmitate-induced cytotoxicity and activation of caspases. Finally, β-cell cytotoxicity caused by the combination of anti-Fas and palmitate at 25 mmol/l of glucose was greater than the sum of those induced by each. These observations suggest that palmitate induces sequential activation of caspase-6 and caspase-3 through a mitochondrial signal(s), and caspase-6 plays a primary role in the mechanism. Fas-mediated β-cell death and lipotoxicity may share common mechanisms involving caspase activation, and thereby synergistically inducing β-cell death, although upstream signaling pathways are distinct.
Journal: Life Sciences - Volume 79, Issue 13, 22 August 2006, Pages 1312–1316