Induction and suppression of endothelial cell apoptosis by sphingolipids: a possible in vitro model for cell-cell interactions between platelets and endothelial cells
| Autor: | Masako Mitsumata, Nobuo Hisano, Shigeo Akimoto, Kaneo Satoh, Yukio Ozaki, Masayuki A. Fujino, Yutaka Yatomi |
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| Rok vydání: | 1999 |
| Předmět: |
Blood Platelets
Ceramide Umbilical Veins Acylation Immunology Acetic Anhydrides Apoptosis Cell Communication Biology Biochemistry Umbilical vein chemistry.chemical_compound Cell–cell interaction Sphingosine Humans Platelet Platelet activation Sphingolipids Cell Biology Hematology DNA Cell biology Endothelial stem cell chemistry Microscopy Fluorescence embryonic structures cardiovascular system Endothelium Vascular Lysophospholipids Sphingomyelin |
| Zdroj: | Blood. 93(12) |
| ISSN: | 0006-4971 |
| Popis: | Because sphingosine (Sph) is actively incorporated into platelets and rapidly converted to sphingosine 1-phosphate (Sph-1-P), which is then released extracellularly, it is important to study the effects of Sph and Sph-1-P on endothelial cells from the viewpoint of platelet-endothelial cell interaction. In this study, we found that Sph, as well as ceramide, induces apoptosis in human umbilical vein endothelial cells (HUVECs). In contrast, Sph-1-P acts as a HUVEC survival factor; this bioactive lipid was shown to protect HUVECs from apoptosis induced by the withdrawal of growth factors and to stimulate HUVEC DNA synthesis. In metabolic studies, [3H]Sph, incorporated into HUVECs, was converted to [3H]Cer and further to [3H]sphingomyelin in a time-dependent manner, whereas [3H]Sph-1-P formation from [3H]Sph was weak and transient. These findings in HUVECs are very different from those of platelets, which possess a highly active Sph kinase but lack Sph-1-P lyase. As a result, platelets abundantly store Sph-1-P, whereas HUVECs contain much less Sph-1-P. Finally, HUVECs, in contrast to platelets, failed to release Sph-1-P extracellularly, indicating that HUVECs themselves are not able to supply the survival factor Sph-1-P, but receive it from activated platelets. Our results suggest that platelets may maintain the integrity of endothelial cells by incorporating Sph and releasing Sph-1-P. |
| Databáze: | OpenAIRE |
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