Ceramide induces p38 MAPK-dependent apoptosis and Bax translocation via inhibition of Akt in HL-60 cells
- Authors
- Kim, Hae Jong; Oh, Ji Eun; Kim, Sang Woo; Chun, Young Jin; Kim, Mie Young
- Issue Date
- Feb-2008
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- ceramide; apoptosis; p38 MAPK; Akt; Bax; HL-60 cells
- Citation
- CANCER LETTERS, v.260, no.1-2, pp 88 - 95
- Pages
- 8
- Journal Title
- CANCER LETTERS
- Volume
- 260
- Number
- 1-2
- Start Page
- 88
- End Page
- 95
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/23842
- DOI
- 10.1016/j.canlet.2007.10.030
- ISSN
- 0304-3835
1872-7980
- Abstract
- Ceramide induces apoptosis through caspase activation, cytochrome c release, and Bax translocation in HL-60 cells. However, the upstream signal transduction pathways that induce Bax translocation during ceramide-mediated apoptosis have not been well defined yet. In this study, the activation of p38 mitogen-activated protein kinase (MAPK) was found to be critical for the induction of apoptosis and subcellular redistribution of Bax. Pharmacological inhibition of p38 MAPK with SB203580 or expression of a dominant-negative p38 MAPK attenuated DNA fragmentation, caspase-3 activation, and Bax translocation in response to ceramide. Overexpression of Akt also led to suppression of Bax translocation to mitochondria during ceramide-induced apoptosis in HL-60 cells. We also provide evidence for cross-talk between p38 MAPK and Akt pathways. Expression of myr-Akt or inhibition of phosphatidylinositol 3-kinase (PI3K) with LY294002 had no effect on p38 MAPK activation by ceramide as assessed by phosphorylation, while inhibition of p38 MAPK by a pharmacological inhibitor or a dominant-negative p38 inhibited Akt dephosphorylation in response to ceramide, suggesting that ceramide-induced p38 MAPK activation negatively regulates the Akt pathway. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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