HDL-associated ApoM is anti-apoptotic by delivering sphingosine 1-phosphate to S1P1 & S1P3 receptors on vascular endothelium
(2017) In Lipids in Health and Disease 16(1).- Abstract
Background: High-density Lipoprotein (HDL) attenuates endothelial cell apoptosis induced by different cell-death stimuli such as oxidation or growth factor deprivation. HDL is the main plasma carrier of the bioactive lipid sphingosine 1-phosphate (S1P), which it is a signaling molecule that promotes cell survival in response to several apoptotic stimuli. In HDL, S1P is bound to Apolipoprotein M (ApoM), a Lipocalin that is only present in around 5% of the HDL particles. The goal of this study is to characterize ApoM-bound S1P role in endothelial apoptosis protection and the signaling pathways involved. Methods: Human umbilical vein endothelial cells (HUVEC) cultures were switched to serum/grow factor deprivation medium to induce... (More)
Background: High-density Lipoprotein (HDL) attenuates endothelial cell apoptosis induced by different cell-death stimuli such as oxidation or growth factor deprivation. HDL is the main plasma carrier of the bioactive lipid sphingosine 1-phosphate (S1P), which it is a signaling molecule that promotes cell survival in response to several apoptotic stimuli. In HDL, S1P is bound to Apolipoprotein M (ApoM), a Lipocalin that is only present in around 5% of the HDL particles. The goal of this study is to characterize ApoM-bound S1P role in endothelial apoptosis protection and the signaling pathways involved. Methods: Human umbilical vein endothelial cells (HUVEC) cultures were switched to serum/grow factor deprivation medium to induce apoptosis and the effect caused by the addition of ApoM and S1P analyzed. Results: The addition of HDL+ApoM or recombinant ApoM-bound S1P promoted cell viability and blocked apoptosis, whereas HDL-ApoM had no protective effect. Remarkably, S1P exerted a more potent anti-apoptotic effect when carried by ApoM as compared to albumin, or when added as free molecule. Mechanistically, cooperation between S1P1 and S1P3 was required for the HDL/ApoM/S1P-mediated anti-apoptotic ability. Furthermore, AKT and ERK phosphorylation was also necessary to achieve the anti-apoptotic effect of the HDL/ApoM/S1P complex. Conclusions: Altogether, our results indicate that ApoM and S1P are key elements of the anti-apoptotic activity of HDL and promote optimal endothelial function.
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- author
- Ruiz Garcia, Mario LU ; Okada, Hiromi and Dahlbäck, Björn LU
- organization
- publishing date
- 2017-02-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- ApoM, Apoptosis, Endothelial cells, HDL, Lipocalins, Sphingosine 1-phospate
- in
- Lipids in Health and Disease
- volume
- 16
- issue
- 1
- article number
- 36
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:28179022
- wos:000396784900001
- scopus:85011655584
- ISSN
- 1476-511X
- DOI
- 10.1186/s12944-017-0429-2
- language
- English
- LU publication?
- yes
- id
- 4a585692-bb31-4dfa-bb60-f8725611b423
- date added to LUP
- 2017-02-20 09:31:45
- date last changed
- 2024-03-31 03:44:58
@article{4a585692-bb31-4dfa-bb60-f8725611b423,
abstract = {{<p>Background: High-density Lipoprotein (HDL) attenuates endothelial cell apoptosis induced by different cell-death stimuli such as oxidation or growth factor deprivation. HDL is the main plasma carrier of the bioactive lipid sphingosine 1-phosphate (S1P), which it is a signaling molecule that promotes cell survival in response to several apoptotic stimuli. In HDL, S1P is bound to Apolipoprotein M (ApoM), a Lipocalin that is only present in around 5% of the HDL particles. The goal of this study is to characterize ApoM-bound S1P role in endothelial apoptosis protection and the signaling pathways involved. Methods: Human umbilical vein endothelial cells (HUVEC) cultures were switched to serum/grow factor deprivation medium to induce apoptosis and the effect caused by the addition of ApoM and S1P analyzed. Results: The addition of HDL+ApoM or recombinant ApoM-bound S1P promoted cell viability and blocked apoptosis, whereas HDL-ApoM had no protective effect. Remarkably, S1P exerted a more potent anti-apoptotic effect when carried by ApoM as compared to albumin, or when added as free molecule. Mechanistically, cooperation between S1P1 and S1P3 was required for the HDL/ApoM/S1P-mediated anti-apoptotic ability. Furthermore, AKT and ERK phosphorylation was also necessary to achieve the anti-apoptotic effect of the HDL/ApoM/S1P complex. Conclusions: Altogether, our results indicate that ApoM and S1P are key elements of the anti-apoptotic activity of HDL and promote optimal endothelial function.</p>}},
author = {{Ruiz Garcia, Mario and Okada, Hiromi and Dahlbäck, Björn}},
issn = {{1476-511X}},
keywords = {{ApoM; Apoptosis; Endothelial cells; HDL; Lipocalins; Sphingosine 1-phospate}},
language = {{eng}},
month = {{02}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Lipids in Health and Disease}},
title = {{HDL-associated ApoM is anti-apoptotic by delivering sphingosine 1-phosphate to S1P1 & S1P3 receptors on vascular endothelium}},
url = {{http://dx.doi.org/10.1186/s12944-017-0429-2}},
doi = {{10.1186/s12944-017-0429-2}},
volume = {{16}},
year = {{2017}},
}