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Ceramide kinase deficiency impairs microendothelial cell angiogenesis in vitro.

Niwa, Satoru and Graf, Christine and Bornancin, Frederic (2009) Ceramide kinase deficiency impairs microendothelial cell angiogenesis in vitro. Microvascular Research, 77 (3). pp. 389-393. ISSN 1095-9319

Abstract

The recent generation of ceramide kinase (CerK)-deficient (Cerk (-/-)) mice as well as the identification of the potent CerK inhibitor NVP-231 have provided unprecedented opportunities to better understand CerK biology. Here we used skin dermal microendothelial cells (DMECs) and we show that CerK activity regulates their neovascularization in a matrigel environment in vitro. Capillary-like tube formation was significantly impaired in CerK-deficient cells or in wild-type (WT) cells treated with NVP-231 as compared with untreated WT cells. This was not the result of compromised proliferation or survival because Cerk (-/-) endothelial cells were able to migrate out of dermal fragments and grow in monolayer culture as well as their WT counterpart. Vascular endothelial growth factor, fibroblast growth factor or tumor necrosis factor could not rescue the angiogenesis defect observed in Cerk (-/-) DMEMs. Moreover, CerK ablation increased serum ceramide levels at the expense of dihydroceramide levels without affecting sphingosine, dihydrosphingosine, sphingosine-1-phosphate or dihydrosphingosine-1-phosphate levels. These observations collectively suggest that CerK-catalyzed formation of C1P may regulate angiogenesis by a novel mechanism that is independent of S1P formation and signaling.

Item Type: Article
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Keywords: Angiogenesis; Ceramide; Ceramide kinase; Ceramide-1-phosphate Sphingosine-1-phosphate VEGF
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Date Deposited: 14 Dec 2009 13:47
Last Modified: 31 Jan 2013 00:49
URI: https://oak.novartis.com/id/eprint/1856

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