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1-desoxysphinganine 1-phosphonate
competitive inhibitor
2-acetyl-4-(1R,2S,3R,4-tetrahydroxybutyl)-imidazole
-
2-vinyl dihydrosphingosine
-
4'-deoxypyridoxine
a pyridoxal 5'-phosphate analog
N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopentenyl)ethyl]octanamide
-
[2-amino-2[2-(4-octylphenyl)ethyl]-3-hydroxypropyl]dihydrogen phosphate
-
(1R,2S,3R)-1-(1H,1'H-2,2'-biimidazol-4-yl)butane-1,2,3,4-tetraol
-
inhibitory to sphinganine 1-phosphate lyase. 53% decrease in circulating lymphocytes after 30 mg/kg oral dose
(1R,2S,3R)-1-(2-(1-benzyl-1H-1,2,4-triazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol
-
inhibitory to sphinganine 1-phosphate lyase. 41% decrease in circulating lymphocytes after 30 mg/kg oral dose
(1R,2S,3R)-1-(2-(thiazol-4-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol
-
inhibitory to sphinganine 1-phosphate lyase. 33% decrease in circulating lymphocytes after 30 mg/kg oral dose
1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone
-
inhibitory to sphinganine 1-phosphate lyase. 25% decrease in circulating lymphocytes after 30 mg/kg oral dose
1-{5-[(1R,2S,3R)-1,2,3,4-tetrahydroxybutyl]-1H-imidazol-2-yl}ethanone
-
when given overnight at 25 mg/l in drinking water, tetrahydroxybutylimidazole raises sphingosine 1-phosphate levels and reduces SPL activity
2-acetyl-4-(tetrahydroxybutyl)imidazole
-
the enzyme is inhibited indirectly by 2-acetyl-4-(tetrahydroxybutyl)imidazole under conditions of vitamin B6 deficiency
2-acetyl-4-tetrahydroxybutylimidazole
-
-
deoxypyridoxine
-
competitive inhibitor
Deoxypyridoxine phosphate
-
-
fumonisin B1
-
10 mg/kg inhibits the expression of sphingosine 1-phosphate lyase
[(4-benzyl-phthalazin-1-yl)-2-methylpiperazin-1-yl]-nicotinonitrile
-
-
FTY720
-
-
FTY720
-
in vivo enzyme inhibition concommitantly with lymphopenia, neither enzyme gene expression nor tissue enzyme protein expression is affected by inhibior
FTY720
-
40% inhibition at 0.03 mM
FTY720
-
produces an 82% inhibition at equimolar concentration with C17-sphinganine-1-phosphate
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metabolism
-
S1P lyase catalyzes the irreversible degradation of sphingosine 1-phosphate in the final step of sphingolipid metabolism
physiological function
all S1PL-deficient genetic models used display lymphopenia, with sequestration of mature T-cells in the thymus and lymph nodes. In addition to the lymphoid phenotypes, S1PL KO mice also develop myeloid cell hyperplasia and significant lesions in the lung, heart, urinary tract, and bone, and have a markedly reduced life span. Complete absence of S1PL affects both maturation/development and egress of mature T cells from the thymus, whereas low level S1PL activity affects T-cell egress more than differentiation
physiological function
SPL is the final enzyme in the sphingolipid degradative pathway and an important regulator of sphingosine 1-phosphate as well as the levels of other sphingolipid intermediates which influence various aspects of cell growth, proliferation and death. SPL is necessary for maintaining lipid homeostasis and appropriate cell fate responses. SPL serves as a therapeutic target for immune modulation
physiological function
a myoblast sphingosine-1-phosphate lyase-knockdown cell accumulates intracellular and extracellular sphingosine-1-phosphate and fails to form myotubes under conditions that normally stimulate myogenic differentiation. Under differentiation conditions, knockdown cells also demonstrate delayed induction of myogenic microRNAs, miR-1, miR-206, and miR-486. Knockdown cells successfully differentiate when treated with an S1P1 agonist, S1P2 antagonist, and combination treatments, which also increase myogenic miRNA levels. Knockdown cells transfected with mimics for miR-1 or miR-206 also overcome the differentiation block
malfunction
-
downregulation/inhibition of SPL prevents premature cell cycle progression and mitotic death. Oral administration of an SPL inhibitor to mice prolonges their survival after exposure to a lethal dose (10Gy) of total body ionizing radiation
malfunction
-
hearts of heterozygous SPL knockout mice exhibit reduced SPL activity, elevated sphingosine 1-phosphate levels, smaller infarct size, and increased functional recovery after ischemia-reperfusion injury compared with littermate controls
malfunction
-
enzyme inhibition causes protein-losing glomerulopathy due to podocyte dysfunction, skin irritation, and platelet activation and may also be associated with pathological alterations in other tissues such as lung, liver, thymus, and the red blood cell system
physiological function
-
complete loss of SPL activity leads to upregulation of the antiapoptotic proteins Bcl-2 and Bcl-xL and consequently protects against apoptosis induced by chemotherapy and nutrient starvation but not against autophagy. Disruption of the gene encoding SPL is accompanied by concomitant accumulation of sphingosine and ceramide. SPL deficiency blocks the apoptotic cascade upstream of mitochondrial damage and leads to upregulation of the antiapoptotic proteins Bcl-2 and Bcl-xL without affecting the levels of the proapoptotic members Bax and Bid. Whereas starvation-induced apoptosis is reduced in Sgpl1-/- compared to Sgpl1+/+ cells, autophagy is similar in both cell types
physiological function
-
in mice with an inactive S1P lyase gene, in addition to the expected increase of sphingoid base phosphates, other sphingolipids including sphingosine, ceramide, and sphingomyelin are substantially elevated in the serum and/or liver. The S1P lyase deficiency results in changes in the levels of serum and liver lipids not directly within the sphingolipid pathway, including phospholipids, triacyglycerol, diacylglycerol, and cholesterol. Lipids in serum and lipid storage are elevated in liver, but adiposity is reduced in the S1P lyase-deficient mice. The S1P lyase deficiency causes widespread changes in the expression pattern of lipid metabolism genes, with a significant increase in the expression of PPAR, a master transcriptional regulator of lipid metabolism. The mRNA expression of the genes encoding the sphingosine kinases and S1P phosphatases, which directly control the levels of S1P, are not significantly changed in liver of the S1P lyase-deficient mice
physiological function
-
in mouse embryonic fibroblasts deficient in S1P lyase, sphingosine 1-phosphate and sphingosine concentrations are elevated about 6fold and 2fold, respectively. Resting intracellular Ca2+ is elevated and agonist-induced intracellular Ca2+ increases are augmented in S1P lyase-deficient cells both in the presence and absence of extracellular Ca2+. Intracellular Ca2+ increases and Ca2+ mobilization induced by the SERCA inhibitor, thapsigargin, are augmented. At least two cell types can be distinguished, one with a rapid and transient intracellular Ca2+-increase and the other with a slower and prolonged intracellular Ca2+ elevation upon stimulation with thapsigargin. Intracellular Ca2+ increases upon thapsigargin stimulation, reflecting overall Ca2+ release, by more than 50% in both rapidly and slowly responding S1P lyase-deficient cells
physiological function
-
incubation of lyase-deficient neurons with either sphingosine or S1P results in a similar elevation in cellular S1P, but only S1P addition to the culture medium induces apoptosis. This is not due to S1P acting on the S1P receptor but to hydrolysis of S1P to sphingosine that is phosphorylated by the cells. Although the cells produce S1P from both exogenously added sphingosine as well as sphingosine derived from exogenous S1P, the S1P from these two sources are not equivalent, because the former is primarily produced by SK1, whereas the latter is mainly formed by sphingosine kinase-2
physiological function
-
thymocyte development in SGPL1-deficient mice which exhibit postnatal discontinuation of early thymocytopoies is starting at 2 weeks after birth. SGPL-/- thymi show a loss of developing thymocytes in the thymic cortex between 2 and 4 weeks of age, whereas mature thymocytes accumulate in the medulla. Increased ceramide levels in the thymus of SGPL1-/- mice abrogates thymic development postnatally by enhanced thymocyte apoptosis and depletion of thymic ETP. Potentially therapeutic immunosuppression by SGPL1 inhibition should benefit from monitoring ceramides to prevent their increase to apoptosis-inducing levels
physiological function
-
SPL contributes to oxidative stress by depleting sphingosine 1-phosphate pools available for cardioprotective signaling
physiological function
-
SPL modulates the kinetics of DNA repair, speed of recovery from G2 cell cycle arrest and the extent of apoptosis after ionizing radiation. SPL expression affects the Cdk1-cyclin B complex
physiological function
-
inducible sphingosine-1-phosphate lyase knockout mice featuring partial reduction of sphingosine-1-phosphate lyase activity are viable but feature profound reduction of peripheral T cells, similar to the constitutive knockout mice. While thymic T cell development in these mice appears normal, mature T cells are retained in thymus and lymph nodes, leading to reduced T cell numbers in spleen and blood, with a skewing towards increased proportions of memory T cells and T regulatory cells. The inducible knockout mice are protected in experimental autoimmune encephalomyelitis. T cell immigration into the CNS is profoundly reduced
physiological function
-
sphingosine phosphate lyase knockdown via short hairpin RNA in embryonic stem cells shows a 5fold increase in cellular sphingosine 1-phosphate levels, increased proliferation rates and high expression of cell surface pluripotency markers SSEA1 and OCT4 compared to vector control cells. Knockdown cells show robust activation of STAT3 and a 10fold increase in S1P2 expression. Inhibition of S1P2 or STAT3 reverses the proliferation and pluripotency phenotypes of knockdown cells. Inhibition of S1P2 attenuates, in a dose-dependent fashion, the high levels of OCT4 and STAT3 activation. Knockdown cells are capable of generating embryoid bodies from which muscle stem cells, called satellite cells, can be isolated
physiological function
-
enzyme expression in mature T cells contributes to efficient thymic egress
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Van Veldhoven, P.P.
Sphingosine-phosphate lyase
Adv. Lipid Res.
26
69-98
1993
Canis lupus familiaris, Cavia porcellus, Homo sapiens, Platyrrhini, Mus musculus, Rattus norvegicus, Sus scrofa, Tetrahymena pyriformis
brenda
Zhou, J.; Saba, J.D.
Identification of the first mammalian sphingosine phosphate lyase gene and its functional expression in yeast
Biochem. Biophys. Res. Commun.
242
502-507
1998
Mus musculus (Q8R0X7), Mus musculus
brenda
Kihara, A.; Ikeda, M.; Kariya, Y.; Lee, E.Y.; Lee, Y.M.; Igarashi, Y.
Sphingosine-1-phosphate lyase is involved in the differentiation of F9 embryonal carcinoma cells to primitive endoderm
J. Biol. Chem.
278
14578-14585
2003
Mus musculus
brenda
Van Veldhoven, P.P.
Sphingosine-1-phosphate lyase
Methods Enzymol.
311
244-254
2000
Homo sapiens, Mammalia, Mus musculus, Rattus norvegicus, Tetrahymena pyriformis
brenda
Ikeda, M.; Kihara, A.; Igarashi, Y.
Sphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5'-phosphate binding domain exposed to the cytosol
Biochem. Biophys. Res. Commun.
325
338-343
2004
Mus musculus
brenda
Ikeda, M.; Kihara, A.; Kariya, Y.; Lee, Y.M.; Igarashi, Y.
Sphingolipid-to-glycerophospholipid conversion in SPL-null cells implies the existence of an alternative isozyme
Biochem. Biophys. Res. Commun.
329
474-479
2005
Mus musculus
brenda
Bandhuvula, P.; Tam, Y.Y.; Oskouian, B.; Saba, J.D.
The immune modulator FTY720 inhibits sphingosine-1-phosphate lyase activity
J. Biol. Chem.
280
33697-33700
2005
Homo sapiens, Mus musculus
brenda
Kim, D.H.; Lee, Y.S.; Lee, Y.M.; Oh, S.; Yun, Y.P.; Yoo, H.S.
Elevation of sphingoid base 1-phosphate as a potential contributor to hepatotoxicity in fumonisin B1-exposed mice
Arch. Pharm. Res.
30
962-969
2007
Mus musculus
brenda
Bandhuvula, P.; Fyrst, H.; Saba, J.D.
A rapid fluorescence assay for sphingosine-1-phosphate lyase enzyme activity
J. Lipid Res.
48
2769-2778
2007
Homo sapiens, Mus musculus
brenda
Oskouian, B.; Sooriyakumaran, P.; Borowsky, A.D.; Crans, A.; Dillard-Telm, L.; Tam, Y.Y.; Bandhuvula, P.; Saba, J.D.
Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer
Proc. Natl. Acad. Sci. USA
103
17384-17389
2006
Homo sapiens, Mus musculus
brenda
Bandhuvula, P.; Saba, J.D.
Sphingosine-1-phosphate lyase in immunity and cancer: silencing the siren
Trends Mol. Med.
13
210-217
2007
Caenorhabditis elegans, Dictyostelium discoideum, Drosophila melanogaster, Homo sapiens, Leishmania major, Mus musculus, Rattus norvegicus
brenda
Colie, S.; Codogno, P.; Levade, T.; Andrieu-Abadie, N.
Regulation of cell death by sphingosine 1-phosphate lyase
Autophagy
6
426-427
2010
Mus musculus
brenda
Claas, R.F.; ter Braak, M.; Hegen, B.; Hardel, V.; Angioni, C.; Schmidt, H.; Jakobs, K.H.; Van Veldhoven, P.P.; zu Heringdorf, D.M.
Enhanced Ca2+ storage in sphingosine-1-phosphate lyase-deficient fibroblasts
Cell. Signal.
22
476-483
2010
Mus musculus
brenda
Hagen, N.; Van Veldhoven, P.P.; Proia, R.L.; Park, H.; Merrill, A.H.; van Echten-Deckert, G.
Subcellular origin of sphingosine 1-phosphate is essential for its toxic effect in lyase-deficient neurons
J. Biol. Chem.
284
11346-11353
2009
Mus musculus
brenda
Bektas, M.; Allende, M.L.; Lee, B.G.; Chen, W.; Amar, M.J.; Remaley, A.T.; Saba, J.D.; Proia, R.L.
Sphingosine 1-phosphate lyase deficiency disrupts lipid homeostasis in liver
J. Biol. Chem.
285
10880-10889
2010
Mus musculus
brenda
Weber, C.; Krueger, A.; Muenk, A.; Bode, C.; Van Veldhoven, P.P.; Graeler, M.H.
Discontinued postnatal thymocyte development in sphingosine 1-phosphate-lyase-deficient mice
J. Immunol.
183
4292-4301
2009
Mus musculus
brenda
Bagdanoff, J.T.; Donoviel, M.S.; Nouraldeen, A.; Tarver, J.; Fu, Q.; Carlsen, M.; Jessop, T.C.; Zhang, H.; Hazelwood, J.; Nguyen, H.; Baugh, S.D.; Gardyan, M.; Terranova, K.M.; Barbosa, J.; Yan, J.; Bednarz, M.; Layek, S.; Courtney, L.F.; Taylor, J.; Digeorge-Foushee, A.M.; Gopinathan, S.; Bruce, D.; Smi, S.m.i.t.
Inhibition of sphingosine-1-phosphate lyase for the treatment of autoimmune disorders
J. Med. Chem.
52
3941-3953
2009
Mus musculus
brenda
Vogel, P.; Donoviel, M.S.; Read, R.; Hansen, G.M.; Hazlewood, J.; Anderson, S.J.; Sun, W.; Swaffield, J.; Oravecz, T.
Incomplete inhibition of sphingosine 1-phosphate lyase modulates immune system function yet prevents early lethality and non-lymphoid lesions
PLoS ONE
4
e4112
2009
Homo sapiens, Mus musculus (Q8R0X7), Mus musculus
brenda
Serra, M.; Saba, J.
Sphingosine 1-phosphate lyase, a key regulator of sphingosine 1-phosphate signaling and function
Adv. Enzyme Regul.
50
349-362
2010
Homo sapiens, Rattus norvegicus, Mus musculus (Q8R0X7)
brenda
Bandhuvula, P.; Honbo, N.; Wang, G.Y.; Jin, Z.Q.; Fyrst, H.; Zhang, M.; Borowsky, A.D.; Dillard, L.; Karliner, J.S.; Saba, J.D.
S1P lyase: a novel therapeutic target for ischemia-reperfusion injury of the heart
Am. J. Physiol. Heart Circ. Physiol.
300
H1753-H1761
2011
Mus musculus
brenda
Berdyshev, E.V.; Goya, J.; Gorshkova, I.; Prestwich, G.D.; Byun, H.S.; Bittman, R.; Natarajan, V.
Characterization of sphingosine-1-phosphate lyase activity by electrospray ionization-liquid chromatography/tandem mass spectrometry quantitation of (2E)-hexadecenal
Anal. Biochem.
408
12-18
2011
Mus musculus
brenda
Kumar, A.; Oskouian, B.; Fyrst, H.; Zhang, M.; Paris, F.; Saba, J.D.
S1P lyase regulates DNA damage responses through a novel sphingolipid feedback mechanism
Cell Death Dis.
2
e119
2011
Mus musculus
brenda
Smith, G.S.; Kumar, A.; Saba, J.D.
Sphingosine phosphate lyase regulates murine embryonic stem cell proliferation and pluripotency through an S1P2/STAT3 signaling pathway
Biomolecules
3
351-368
2013
Mus musculus
brenda
Reina, E.; Camacho, L.; Casas, J.; Van Veldhoven, P.P.; Fabrias, G.
Determination of sphingosine-1-phosphate lyase activity by gas chromatography coupled to electron impact mass spectrometry
Chem. Phys. Lipids
165
225-231
2012
Mus musculus
brenda
de la Garza-Rodea, A.S.; Baldwin, D.M.; Oskouian, B.; Place, R.F.; Bandhuvula, P.; Kumar, A.; Saba, J.D.
Sphingosine phosphate lyase regulates myogenic differentiation via S1P receptor-mediated effects on myogenic microRNA expression
FASEB J.
28
506-519
2014
Mus musculus (Q8R0X7), Mus musculus
brenda
Borowsky, A.D.; Bandhuvula, P.; Kumar, A.; Yoshinaga, Y.; Nefedov, M.; Fong, L.G.; Zhang, M.; Baridon, B.; Dillard, L.; de Jong, P.; Young, S.G.; West, D.B.; Saba, J.D.
Sphingosine-1-phosphate lyase expression in embryonic and adult murine tissues
J. Lipid Res.
53
1920-1931
2012
Mus musculus
brenda
Billich, A.; Baumruker, T.; Beerli, C.; Bigaud, M.; Bruns, C.; Calzascia, T.; Isken, A.; Kinzel, B.; Loetscher, E.; Metzler, B.; Mueller, M.; Nuesslein-Hildesheim, B.; Kleylein-Sohn, B.
Partial deficiency of sphingosine-1-phosphate lyase confers protection in experimental autoimmune encephalomyelitis
PLoS ONE
8
e59630
2013
Mus musculus
brenda
Suh, J.H.; Eltanawy, A.; Rangan, A.; Saba, J.D.
A facile stable-isotope dilution method for determination of sphingosine phosphate lyase activity
Chem. Phys. Lipids
194
101-109
2016
Homo sapiens, Mus musculus
brenda
Zamora-Pineda, J.; Kumar, A.; Suh, J.H.; Zhang, M.; Saba, J.D.
Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress
J. Exp. Med.
213
2773-2791
2016
Mus musculus
brenda
Ohtoyo, M.; Tamura, M.; Machinaga, N.; Muro, F.; Hashimoto, R.
Sphingosine 1-phosphate lyase inhibition by 2-acetyl-4-(tetrahydroxybutyl)imidazole (THI) under conditions of vitamin B6 deficiency
Mol. Cell. Biochem.
400
125-133
2015
Mus musculus
brenda
Schuemann, J.; Grevot, A.; Ledieu, D.; Wolf, A.; Schubart, A.; Piaia, A.; Sutter, E.; Cote, S.; Beerli, C.; Pognan, F.; Billich, A.; Moulin, P.; Walker, U.J.
Reduced activity of sphingosine-1-phosphate lyase induces podocyte-related glomerular proteinuria, skin irritation, and platelet activation
Toxicol. Pathol.
43
694-703
2015
Mus musculus, Rattus norvegicus
brenda