ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Effect of sphingosine kinase 1 inhibition on blood pressure.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Sphingolipid Metabolism and Signaling in Endothelial Cell Functions.Advances in experimental medicine and biology · 2022Review
- Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1.Nature communications · 2020Article
- Regulation of mPGES-1 composition and cell growth via the MAPK signaling pathway in jurkat cells.Experimental and therapeutic medicine · 2018Article
- Genetic deletion of sphingosine kinase 1 suppresses mouse breast tumor development in an HER2 transgenic model.Carcinogenesis · 2018Article
- Vascular transcriptome profiling identifies Sphingosine kinase 1 as a modulator of angiotensin II-induced vascular dysfunction.Scientific reports · 2017Article
- The role of sphingolipid signalling in diabetes‑associated pathologies (Review).International journal of molecular medicine · 2017Review
- S1P Signaling and De Novo Biosynthesis in Blood Pressure Homeostasis.The Journal of pharmacology and experimental therapeutics · 2016Review
- Implication of sphingosin-1-phosphate in cardiovascular regulation.Frontiers in bioscience (Landmark edition) · 2016Review
- PDGF induces SphK1 expression via Egr-1 to promote pulmonary artery smooth muscle cell proliferation.American journal of physiology. Cell physiology · 2016Article
- A novel sphingosine kinase 1 inhibitor (SKI-5C) induces cell death of Wilms' tumor cellsAmerican journal of translational research · 2016Article
- Inhibition of Sphingosine Kinase 1 Ameliorates Angiotensin II-Induced Hypertension and Inhibits Transmembrane Calcium Entry via Store-Operated Calcium Channel.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Switching the sphingolipid rheostat in the treatment of diabetes and cancer comorbidity from a problem to an advantage.BioMed research international · 2015Review
- Sphingosine kinase 1 (Sphk1) negatively regulates platelet activation and thrombus formation.American journal of physiology. Cell physiology · 2014Article
- Sphingosine kinase 1 mediates head & neck squamous cell carcinoma invasion through sphingosine 1-phosphate receptor 1.Cancer cell international · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Accumulating evidence suggests that sphingosine kinase 1 (SphK1) plays a key role in carcinogenesis by regulating cyclooxygenase-2 (COX-2) expression. Recent clinical studies have revealed that COX-2 inhibitors cause adverse cardiovascular side effects, likely due to inhibition of prostacyclin (PGI(2)). In this work, we investigated the roles of SphK1 inhibition on blood pressure (BP). The results show that lack of SphK1 expression did not exacerbate angiotensin II (Ang II)-induced acute hypertension, whereas celecoxib, a COX-2 inhibitor, augmented and sustained higher BP in mice. Interestingly, SphK1-knockout mice inhibited prostaglandin E(2) (PGE(2)) but not PGI(2) production in response to Ang II, whereas celecoxib blocked both PGE(2) and PGI(2) production. Mechanistically, SphK1 down-regulation by siRNA in human umbilical vein endothelial cells decreased cytokine-induced PGE(2) production primarily through inhibition of microsomal PGE synthase-1 (mPGES-1), not COX-2. SphK1 down-regulation also decreased MKK6 expression, which phosphorylates and activates P38 MAPK, which, in turn, regulates early growth response-1 (Egr-1), a transcription factor of mPGES-1. Together, these data indicate that SphK1 regulates PGE(2) production by mPGES-1 expression via the p38 MAPK pathway, independent of COX-2 signaling, in endothelial cells, suggesting that SphK1 inhibition may be a promising strategy for cancer chemoprevention with lack of the adverse cardiovascular side effects associated with coxibs.
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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.