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Gene Review

SGPL1  -  sphingosine-1-phosphate lyase 1

Homo sapiens

Synonyms: KIAA1252, S1PL, SP-lyase 1, SPL, SPL 1, ...
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Disease relevance of SGPL1

  • On the other hand, SPL is downregulated in human colon cancers and in Min mouse adenomas compared to adjacent uninvolved tissues [1].
  • CONCLUSIONS--The increased SPL causes compression atelectasis; this is prevented when PEEP to a given lung region is equal to or greater than the SPL [2].
  • Importantly, SPL expression was significantly down-regulated in human colon cancer tissues in comparison with normal adjacent tissues, as determined by quantitative real-time PCR (Q-PCR) and immunohistochemical analysis [3].
  • We present here the first detailed characterization of catalytically active SP lyase, which has been anaerobically purified from overexpressing Escherichia coli [4].
  • Recently, during the course of a series of experiments on the induction of EAE in SJL/J, PL/J, and (SJL/J X PL/J)F1 (SPL F1) mice, it was observed that the F1 mice frequently had paralytic relapses after recovery from MBP-induced symptoms [5].

Psychiatry related information on SGPL1

  • These units had response latencies between 1.5 and 27 ms and minimum thresholds between 2 and 83.5 dB SPL [6].
  • For animals (N = 48) in the age range of 6-8 months, mean auditory thresholds were about 20 dB SPL between 2.0 and 8.0 kHz, 25 dB at 16 kHz and 30 dB at 1.0 kHz [7].
  • Across-frequency integration of complex signals was investigated by measuring psychometric functions [log (d') versus signal level in dB SPL] for detection of brief and long signals presented in broadband noise [8].
  • For normally hearing subjects tested at a level of 70 dB SPL per component, thresholds for detecting the phase shift [i.e., phase difference limens (DLs)] were smallest (2 degrees-4 degrees) for harmonics above the eighth and for the lowest fundamental frequency (F0) [9].
  • No significant difference in speech perception was obtained for either of the three MAPs when the lower presentation level (55 dB SPL) was used [10].

High impact information on SGPL1

  • Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer [3].
  • Endogenous SPL expression was induced by DNA damage in WT cells, whereas SPL knockdown diminished apoptotic responses [3].
  • The enzyme spore photoproduct lyase (SP lyase) has been found to catalyze the repair of SP dimers to thymine monomers in a reaction that requires S-adenosylmethionine [4].
  • This identifies sphingosine-1-phosphate lyase as a dual modulator of sphingosine 1-phosphate and ceramide metabolism as well as a regulator of cell fate decisions and, hence, a potential target for diseases with an imbalance in these biomodulators, such as cancer [11].
  • Sphingosine-1-phosphate lyase is responsible for the ultimate step in sphingolipid breakdown, converting phosphorylated long chain bases into ethanolamine phosphate and a fatty aldehyde [12].

Chemical compound and disease context of SGPL1

  • The amplitude of the local field potential elicited with 60dB SPL tone bursts increased significantly 2h after salicylate treatment particularly at 16-20kHz; frequencies associated with the tinnitus pitch [13].
  • The combination of cisplatin plus noise produced significantly more hair cell loss and hearing loss at the high frequencies than did either the noise or cisplatin alone when the noise level was 85 dB SPL or higher; no interaction was seen when the noise level was 70 dB SPL [14].
  • Responses of single or multiple neurons were recorded from the inferior colliculus of unanesthetized mustached bats with tungsten-wire electrodes, and their response latencies were measured with tone bursts at their best frequencies and best amplitudes or 65 dB SPL [15].
  • RESULTS: The application of gentamicin caused a frequency-dependent hearing loss that ranged from 24.8 dB SPL at low frequencies to 66.2 dB SPL at high frequencies [16].

Biological context of SGPL1


Anatomical context of SGPL1

  • S1P is irreversibly degraded by S1P lyase (SPL), an enzyme that is highly expressed in enterocytes, where it is involved in metabolism of dietary sphingolipids [1].
  • B and/or null cell-enriched populations severely depleted of T cells (less than 0.7% did not respond to PHA, SPL, or Con A-Sepharose [19].
  • SPL and Con A-Sepharose stimulated DNA synthesis in T cell-enriched cultures if the macrophage content was greater than 1.5%; however, alpha-LT production was not induced by these two mitogens even when reconstituted with 10% macrophages [19].
  • At 6-9 weeks after transplantation, the frequency of transduced human cells in the bone marrow (BM) (40.5% +/- 2.4% [mean +/- SE]) and spleen (SPL) (36.4% +/- 3.2%) in recipients of UCB cells was significantly higher (p < 0.001) than that observed in the BM (2.2% +/- 1.8%) and SPL (2.0% +/- 2.6%) in recipients of MPB [20].
  • In a study on 40 healthy subjects, it was found that sensation seeking is clearly related to the auditory evoked response pattern (N1/P2-component, stimulus intensities: 60, 70, 80, 90, 100 dB SPL) of the superior temporal plane including primary auditory cortex, but not to that of secondary auditory areas in the lateral temporal cortex [21].

Associations of SGPL1 with chemical compounds

  • Sphingosine-1-phosphate lyase is a widely expressed enzyme that catalyzes the essentially irreversible cleavage of the signaling molecule sphingosine 1-phosphate [11].
  • Sphingosine-1-phosphate lyase catalyzes the last step in sphingolipid breakdown, the cleavage of phosphorylated sphingoid bases such as sphingenine-1-phosphate [17].
  • Unlike DNA photolyase, SP lyase does not contain a flavin cofactor and does not require light for activation [22].
  • Reaction of 6-(3)H-SP, but not methyl-(3)H-SP, with SP lyase and AdoMet results in transfer of (3)H to AdoMet, while no tritiated 5'-deoxyadenosine is observed [22].
  • 2. Changes in the multiunit discharge properties after 50-75 mg/kg furosemide injection were as follows: the best frequency (BF) threshold increased from initial values in the range of 20-30 dB SPL to 50-80 dB SPL at 10-20 min postinjection and then recovered fully by 60-90 min [23].

Analytical, diagnostic and therapeutic context of SGPL1


  1. Sphingosine-1-phosphate metabolism and intestinal tumorigenesis: lipid signaling strikes again. Oskouian, B., Saba, J. Cell Cycle (2007) [Pubmed]
  2. Regional effects and mechanism of positive end-expiratory pressure in early adult respiratory distress syndrome. Gattinoni, L., D'Andrea, L., Pelosi, P., Vitale, G., Pesenti, A., Fumagalli, R. JAMA (1993) [Pubmed]
  3. Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer. Oskouian, B., Sooriyakumaran, P., Borowsky, A.D., Crans, A., Dillard-Telm, L., Tam, Y.Y., Bandhuvula, P., Saba, J.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Characterization of an active spore photoproduct lyase, a DNA repair enzyme in the radical S-adenosylmethionine superfamily. Buis, J.M., Cheek, J., Kalliri, E., Broderick, J.B. J. Biol. Chem. (2006) [Pubmed]
  5. Relapsing murine experimental allergic encephalomyelitis induced by myelin basic protein. Fritz, R.B., Chou, C.H., McFarlin, D.E. J. Immunol. (1983) [Pubmed]
  6. Responses of cerebellar neurons of the CF-FM bat, Pteronotus parnellii to acoustic stimuli. Jen, P.H., Sun, X., Kamada, T. Brain Res. (1982) [Pubmed]
  7. Age-related changes in auditory potentials of Mongolian gerbil. Mills, J.H., Schmiedt, R.A., Kulish, L.F. Hear. Res. (1990) [Pubmed]
  8. Efficient across-frequency integration: evidence from psychometric functions. Hicks, M.L., Buus, S. The Journal of the Acoustical Society of America. (2000) [Pubmed]
  9. Difference limens for phase in normal and hearing-impaired subjects. Moore, B.C., Glasberg, B.R. The Journal of the Acoustical Society of America. (1989) [Pubmed]
  10. Speech perception using maps based on neural response telemetry measures. Seyle, K., Brown, C.J. Ear and hearing. (2002) [Pubmed]
  11. Sphingosine-phosphate lyase enhances stress-induced ceramide generation and apoptosis. Reiss, U., Oskouian, B., Zhou, J., Gupta, V., Sooriyakumaran, P., Kelly, S., Wang, E., Merrill, A.H., Saba, J.D. J. Biol. Chem. (2004) [Pubmed]
  12. Subcellular localization and membrane topology of sphingosine-1-phosphate lyase in rat liver. Van Veldhoven, P.P., Mannaerts, G.P. J. Biol. Chem. (1991) [Pubmed]
  13. Salicylate induced tinnitus: Behavioral measures and neural activity in auditory cortex of awake rats. Yang, G., Lobarinas, E., Zhang, L., Turner, J., Stolzberg, D., Salvi, R., Sun, W. Hear. Res. (2007) [Pubmed]
  14. Interaction of cisplatin and noise on the peripheral auditory system. Gratton, M.A., Salvi, R.J., Kamen, B.A., Saunders, S.S. Hear. Res. (1990) [Pubmed]
  15. The inferior colliculus of the mustached bat has the frequency-vs-latency coordinates. Hattori, T., Suga, N. J. Comp. Physiol. A (1997) [Pubmed]
  16. Brain-derived neurotrophic factor treatment does not improve functional recovery after hair cell regeneration in the pigeon. Radeloff, A., Smolders, J.W. Acta Otolaryngol. (2006) [Pubmed]
  17. Human sphingosine-1-phosphate lyase: cDNA cloning, functional expression studies and mapping to chromosome 10q22(1). Van Veldhoven, P.P., Gijsbers, S., Mannaerts, G.P., Vermeesch, J.R., Brys, V. Biochim. Biophys. Acta (2000) [Pubmed]
  18. Bicistronic retroviral vector reveals capacity of v-erbA to induce erythroleukemia and to co-operate with v-myb. Casini, T., Graf, T. Oncogene (1995) [Pubmed]
  19. Cytotoxic activity of lymphocytes. VII. cellular origin of alpha-lymphotoxin. Yano, K., Lucas, Z.J. J. Immunol. (1978) [Pubmed]
  20. Differential transduction efficiency of SCID-repopulating cells derived from umbilical cord blood and granulocyte colony-stimulating factor-mobilized peripheral blood. Pollok, K.E., van Der Loo, J.C., Cooper, R.J., Hartwell, J.R., Miles, K.R., Breese, R., Williams, E.P., Montel, A., Seshadri, R., Hanenberg, H., Williams, D.A. Hum. Gene Ther. (2001) [Pubmed]
  21. Sensory cortical processing and the biological basis of personality. Hegerl, U., Gallinat, J., Mrowinski, D. Biol. Psychiatry (1995) [Pubmed]
  22. Direct H atom abstraction from spore photoproduct C-6 initiates DNA repair in the reaction catalyzed by spore photoproduct lyase: evidence for a reversibly generated adenosyl radical intermediate. Cheek, J., Broderick, J.B. J. Am. Chem. Soc. (2002) [Pubmed]
  23. Effects of furosemide on distortion product otoacoustic emissions and on neuronal responses in the anteroventral cochlear nucleus. Rübsamen, R., Mills, D.M., Rubel, E.W. J. Neurophysiol. (1995) [Pubmed]
  24. Fine structure of degeneration in the cochlear nucleus of the chinchilla after acoustic overstimulation. Kim, J.J., Gross, J., Potashner, S.J., Morest, D.K. J. Neurosci. Res. (2004) [Pubmed]
  25. Intensity coding of auditory stimuli: an fMRI study. Jäncke, L., Shah, N.J., Posse, S., Grosse-Ryuken, M., Müller-Gärtner, H.W. Neuropsychologia. (1998) [Pubmed]
  26. Discharge properties of pigeon single auditory nerve fibers after recovery from severe acoustic trauma. Müller, M., Smolders, J.W., Ding-Pfennigdorff, D., Klinke, R. Int. J. Dev. Neurosci. (1997) [Pubmed]
  27. Sphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5'-phosphate binding domain exposed to the cytosol. Ikeda, M., Kihara, A., Igarashi, Y. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
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