Induction and suppression of endothelial cell apoptosis by sphingolipids: a possible in vitro model for cell-cell interactions between platelets and endothelial cells.
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.
Hisano
N
N
Department of Laboratory Medicine, First Department of Pathology and First Department of Internal Medicine, Yamanashi Medical University, Yamanashi, Japan.
Yatomi
Y
Y
Satoh
K
K
Akimoto
S
S
Mitsumata
M
M
Fujino
M A
MA
Ozaki
Y
Y
D000089:Acetic Anhydrides / Q000378:metabolism; D000215:Acylation; D017209:Apoptosis / Q000187:drug effects*; D001792:Blood Platelets / Q000166:cytology*; D002450:Cell Communication; D004247:DNA / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids; D008856:Microscopy, Fluorescence; D013107:Sphingolipids / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014471:Umbilical Veins
D000089:Acetic Anhydrides; D008246:Lysophospholipids; C064769:N-acetylsphingosine; D013107:Sphingolipids; C060506:sphingosine 1-phosphate; C031800:acetic anhydride; D004247:DNA; D013110:Sphingosine