期刊
JOURNAL OF LIPID RESEARCH
卷 55, 期 8, 页码 1730-1737出版社
ELSEVIER
DOI: 10.1194/jlr.M050021
关键词
high density lipoprotein; kidney; megalin; chloride-proton exchanger ClC5; cystinosin
资金
- Zurich Center of Integrated Human Physiology, University of Zurich (ZIHP)
- Swiss National Science Foundation
- European Commission [305707, 603091]
- Fonds de la Recherche Scientifique (Belgium)
- Fonds de la Recherche Scientifique Medicale (Belgium)
- National Centre of Competence in Research (NCCR) Kidney CH
- Swiss National Science Foundation [310030_143929]
- European Community [305608]
- Swiss National Science Foundation (SNF) [310030_143929] Funding Source: Swiss National Science Foundation (SNF)
Sphingosine-1-phosphate (S1P) mediates several cytoprotective functions of HDL. apoM acts as a S1P binding protein in HDL. Erythrocytes are the major source of S1P in plasma. After glomerular filtration, apoM is endocytosed in the proximal renal tubules. Human or murine HDL elicited time-and dose-dependent S1P efflux from erythrocytes. Compared with HDL of wild-type (wt) mice, S1P efflux was enhanced in the presence of HDL from apoM transgenic mice, but not diminished in the presence of HDL from apoM knockout (Apom(-/-)) mice. Artificially reconstituted and apoM-free HDL also effectively induced S1P efflux from erythrocytes. S1P and apoM were not measurable in the urine of wt mice. Apom(-/-) mice excreted significant amounts of S1P. apoM was detected in the urine of mice with defective tubular endocytosis because of knockout of the LDL receptor-related protein, chloride-proton exchanger ClC-5 (Clcn5(-/-)), or the cysteine transporter cystinosin. Urinary levels of S1P were significantly elevated in Clcn5(-/-) mice. In contrast to Apom(-/-) mice, these mice showed normal plasma concentrations for apoM and S1P. In conclusion, HDL facilitates S1P efflux from erythrocytes by both apoM-dependent and apoM-independent mechanisms. Moreover, apoM facilitates tubular reabsorption of S1P from the urine, however, with no impact on S1P plasma concentrations.
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