کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2052445 | 1074230 | 2005 | 7 صفحه PDF | دانلود رایگان |
In this report, we show for the first time that ceramide-1-phosphate (C1P) stimulates the phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (PKB) pathway, which is a major mechanism whereby growth factors promote cell survival. Also, C1P induced IκB phosphorylation, and enhanced the DNA binding activity of the transcription factor NF-κB. Apoptotic macrophages showed a marked reduction of Bcl-XL levels, and this was prevented by C1P. These findings suggest that C1P blocks apoptosis, at least in part, by stimulating the PI3-K/PKB/ NF-κB pathway and maintaining the production of antiapoptotic Bcl-XL. Based on these and our previous observations, we propose a working model for C1P in which inhibition of acid sphingomyelinase and the subsequent decrease in ceramide levels would allow cell signaling through stimulation of the PI3-K/PKB pathway to promote cell survival.
Journal: FEBS Letters - Volume 579, Issue 17, 4 July 2005, Pages 3744–3750