ArticleThe Biochemical journal2020
Mechanism of sphingosine 1-phosphate clearance from blood.
Article in The Biochemical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 33 citations in OpenAlex.
- Sphingosine kinase 2 regulates adipocyte browning and whole-body metabolism.Science advances · 2026Article
- Article
- Clinical Significance of Plasma Sphingosine-1-Phosphate Decline in Progression of Spinal and Bulbar Muscular Atrophy.Journal of clinical neurology (Seoul, Korea) · 2026Article
- Sphingosine-1-Phosphate Receptor 1 regulates competition dependent astrocyte morphogenesis and tiling in murine cortex.bioRxiv : the preprint server for biology · 2026Article
- Apolipoprotein M: Structural insights, functional roles, and therapeutic approaches in vascular disease.The Journal of biological chemistry · 2026Review
- Blood-borne sphingosine 1-phosphate maintains vascular resistance, blood pressure, and cardiac function in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The contribution of the sphingosine 1-phosphate signaling pathway to chronic kidney diseases: recent findings and new perspectives.Pflugers Archiv : European journal of physiology · 2024Review
- Zonation and ligand and dose dependence of sphingosine 1-phosphate receptor-1 signalling in blood and lymphatic vasculature.Cardiovascular research · 2024Article
- Regulation of cellular and systemic sphingolipid homeostasis.Nature reviews. Molecular cell biology · 2024Review
- Deletion of Sphingosine Kinase 2 Attenuates Acute Kidney Injury in Mice with Hemolytic-Uremic Syndrome.International journal of molecular sciences · 2024Article
- How do sphingosine-1-phosphate affect immune cells to resolve inflammation?Frontiers in immunology · 2024Review
- Sphingosine Kinase 2 in Stromal Fibroblasts Creates a Hospitable Tumor Microenvironment in Breast Cancer.Cancer research · 2023Article
- Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein.Oncogenesis · 2022Article
- The Impact of Sphingosine Kinases on Inflammation-Induced Cytokine Release and Vascular Endothelial Barrier Integrity.International journal of molecular sciences · 2022Article
- Sphingosine Kinase 2 Inhibitors: Rigid Aliphatic Tail Derivatives Deliver Potent and Selective Analogues.ACS bio & med chem Au · 2022Article
- The lymphatic vascular system: much more than just a sewer.Cell & bioscience · 2022Review
- Sphingosine 1-phosphate signaling in perivascular cells enhances inflammation and fibrosis in the kidney.Science translational medicine · 2022Article
- Identification of two lipid phosphatases that regulate sphingosine-1-phosphate cellular uptake and recycling.Journal of lipid research · 2022Article
- Erythrocytes increase endogenous sphingosine 1-phosphate levels as an adaptive response to SARS-CoV-2 infection.Clinical science (London, England : 1979) · 2021Article
- Mouse Liver Compensates Loss of Sgpl1 by Secretion of Sphingolipids into Blood and Bile.International journal of molecular sciences · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The interplay of sphingosine 1-phosphate (S1P) synthetic and degradative enzymes as well as S1P exporters creates concentration gradients that are a fundamental to S1P biology. Extracellular S1P levels, such as in blood and lymph, are high relative to cellular S1P. The blood-tissue S1P gradient maintains endothelial integrity while local S1P gradients influence immune cell positioning. Indeed, the importance of S1P gradients was recognized initially when the mechanism of action of an S1P receptor agonist used as a medicine for multiple sclerosis was revealed to be inhibition of T-lymphocytes' recognition of the high S1P in efferent lymph. Furthermore, the increase in erythrocyte S1P in response to hypoxia influences oxygen delivery during high altitude acclimatization. However, understanding of how S1P gradients are maintained is incomplete. For example, S1P is synthesized but is only slowly metabolized by blood yet circulating S1P turns over quickly by an unknown mechanism. Prompted by the counterintuitive observation that blood S1P increases markedly in response to inhibition S1P synthesis (by sphingosine kinase 2 (SphK2)), we studied mice wherein several tissues were made deficient in either SphK2 or S1P degrading enzymes. Our data reveal a mechanism whereby S1P is de-phosphorylated at the hepatocyte surface and the resulting sphingosine is sequestered by SphK phosphorylation and in turn degraded by intracellular S1P lyase. Thus, we identify the liver as the primary site of blood S1P clearance and provide an explanation for the role of SphK2 in this process. Our discovery suggests a general mechanism whereby S1P gradients are shaped.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.