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LSS  -  lanosterol synthase (2,3-oxidosqualene...

Homo sapiens

Synonyms: 2,3-epoxysqualene--lanosterol cyclase, Lanosterol synthase, OSC, Oxidosqualene--lanosterol cyclase, hOSC
 
 
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Disease relevance of LSS

 

Psychiatry related information on LSS

  • Furthermore, they had longer reaction times, more LSS reactions, smaller toe and heel distances, and larger foot clearances [6].
 

High impact information on LSS

  • Specifically, lanosterol synthase in the sterol biosynthetic pathway was identified as a target of the antianginal drug molsidomine, which may explain its cholesterol-lowering effects [7].
  • Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis [8].
  • OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway [8].
  • The enzyme oxidosqualene:lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia [8].
  • Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages [8].
 

Biological context of LSS

  • In vivo inhibition of 2,3-oxidosqualene:lanosterol cyclase (OSC, E.C. 5.4.99.7)--the enzyme which catalyzes the cyclization of monooxidosqualene to lanosterol--does not result in elevated 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) activity [9].
  • We cloned a portion of the human lanosterol synthase cDNA (almost 85% of the coding region) from a brain cDNA library and determined its nucleotide sequence [10].
  • Using pools of random HC21-specific cosmids from the LL21NC02-Q library and cosmids from 21q22.3 we have identified five different coding regions with strong homology to the lanosterol synthase genes of rat and yeast [10].
  • The human lanosterol synthase gene maps to chromosome 21q22.3 [10].
  • These data suggest that inhibition of OSC by Ro 48-8071 results in an indirect down-regulation of HMGR mRNA levels and synthesis [9].
 

Anatomical context of LSS

  • Using somatic cell hybrids and HC21 yeast artificial chromosomes (YACS) and cosmids, we mapped the human lanosterol synthase cDNA gene to 2lq22.3 between markers D21S25 and 21qter [10].
  • The obtained IC(50) for the reference inhibitor Ro 48-8071 is nearly identical for the recombinant hOSC compared to OSC from human liver microsomes [11].
  • We describe azimuthal light scattering spectroscopy (varphi/LSS), a novel technique for assessing epithelial-cell nuclear morphology [12].
  • METHODS: Sagittal plane video (200 Hz) and EMG from eight lower extremity muscles were recorded during each of three locomotion conditions: incline running at 4.5 m x s(-1) and 30% grade (INC), level running at 4.5 m x s(-1) (LSS), and level running at the same stride frequency as INC (LSSF) [13].
  • The LSS imaging system provides wide-area spectroscopic images of the epithelium, typically 2 cm in each dimension, depicting the size distribution and chromatin content of the cell nuclei, which are key parameters in diagnosing pre-cancer [14].
 

Associations of LSS with chemical compounds

  • We considered LS an excellent candidate HPE gene because of the requirement for cholesterol modification of the Sonic Hedgehog protein for the correct patterning activity of this HPE-associated protein [2].
  • This trait is attributed to increased levels of oxysterols, produced upon partial inhibition of OSC, that suppress HMGR and other sterol-responsive genes [9].
  • The monotopic integral membrane protein 2,3-oxidosqualene cyclase (OSC) catalyzes the formation of lanosterol the first sterol precursor of cholesterol in mammals [11].
  • The yeast lanosterol synthase deficient mutant SMY8 was complemented by the human gene, and a cell-free homogenate of SMY8 expressing the human gene was shown to convert 2,3-oxidosqualene to lanosterol [15].
  • Two novel hypolipidaemic agents, both members of the aminopyrimidine series, with a mode of action of inhibition of oxidosqualene cyclase (OSC), were administered orally to dogs and mice for 14 and 28 days [16].
 

Other interactions of LSS

  • Despite extensive pedigree analysis of numerous polymorphisms, as well as complementation studies in yeast on one of the missense mutations, we find no evidence that the LS gene is in fact HPE1, implicating another gene located in this chromosomal region in HPE pathogenesis [2].
  • Cockerels were kept in environments characterized by high (HSS), medium (MSS), or low (LSS) levels of social stress for 3 or 4 months [1].
  • ECs were kept in static condition or pre-exposed to a high level (HSS, 20 dynes/cm2) or a low level of shear stress (LSS, 0.5 dynes/cm2) for 24 h, and TNF-alpha was added under static condition for 4 h [17].
 

Analytical, diagnostic and therapeutic context of LSS

References

  1. Long-term exposure of chickens to three levels of social stress. Gross, W.B., Siegel, P.B. Avian Dis. (1981) [Pubmed]
  2. Structure of the human Lanosterol synthase gene and its analysis as a candidate for holoprosencephaly (HPE1). Roessler, E., Mittaz, L., Du, Y., Scott, H.S., Chang, J., Rossier, C., Guipponi, M., Matsuda, S.P., Muenke, M., Antonarakis, S.E. Hum. Genet. (1999) [Pubmed]
  3. The role of root exudates in aluminium resistance and silicon-induced amelioration of aluminium toxicity in three varieties of maize (Zea mays L.). Kidd, P.S., Llugany, M., Poschenrieder, C., Gunsé, B., Barceló, J. J. Exp. Bot. (2001) [Pubmed]
  4. Assessment of Leishmaniasis notification system in Santiago del Estero, Argentina, 1990-1993. Yadón, Z.E., Quigley, M.A., Davies, C.R., Rodrigues, L.C., Segura, E.L. Am. J. Trop. Med. Hyg. (2001) [Pubmed]
  5. Laurin-Sandrow syndrome with additional associated manifestations. Kantaputra, P.N. Am. J. Med. Genet. (2001) [Pubmed]
  6. Advancing age progressively affects obstacle avoidance skills in the elderly. Weerdesteyn, V., Nienhuis, B., Duysens, J. Human movement science. (2005) [Pubmed]
  7. Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes. Lum, P.Y., Armour, C.D., Stepaniants, S.B., Cavet, G., Wolf, M.K., Butler, J.S., Hinshaw, J.C., Garnier, P., Prestwich, G.D., Leonardson, A., Garrett-Engele, P., Rush, C.M., Bard, M., Schimmack, G., Phillips, J.W., Roberts, C.J., Shoemaker, D.D. Cell (2004) [Pubmed]
  8. Lord of the rings--the mechanism for oxidosqualene:lanosterol cyclase becomes crystal clear. Huff, M.W., Telford, D.E. Trends Pharmacol. Sci. (2005) [Pubmed]
  9. Down-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels and synthesis in syrian hamster C100 cells by the oxidosqualene cyclase inhibitor [4'-(6-allyl-ethyl-amino-hexyloxy)-2'-fluoro-phenyl]-(4-bromophenyl)-me thanone (Ro 48-8071): comparison to simvastatin. Peffley, D.M., Gayen, A.K., Morand, O.H. Biochem. Pharmacol. (1998) [Pubmed]
  10. The human lanosterol synthase gene maps to chromosome 21q22.3. Young, M., Chen, H., Lalioti, M.D., Antonarakis, S.E. Hum. Genet. (1996) [Pubmed]
  11. The monotopic membrane protein human oxidosqualene cyclase is active as monomer. Ruf, A., Müller, F., D'Arcy, B., Stihle, M., Kusznir, E., Handschin, C., Morand, O.H., Thoma, R. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  12. Assessing epithelial cell nuclear morphology by using azimuthal light scattering spectroscopy. Yu, C.C., Lau, C., Tunnell, J.W., Hunter, M., Kalashnikov, M., Fang-Yen, C., Fulghum, S.F., Badizadegan, K., Dasari, R.R., Feld, M.S. Optics letters. (2006) [Pubmed]
  13. An integrated biomechanical analysis of high speed incline and level treadmill running. Swanson, S.C., Caldwell, G.E. Medicine and science in sports and exercise. (2000) [Pubmed]
  14. Spectroscopic diagnosis and imaging of invisible pre-cancer. Badizadegan, K., Backman, V., Boone, C.W., Crum, C.P., Dasari, R.R., Georgakoudi, I., Keefe, K., Munger, K., Shapshay, S.M., Sheetse, E.E., Feld, M.S. Faraday Discuss. (2004) [Pubmed]
  15. Molecular cloning of the human gene encoding lanosterol synthase from a liver cDNA library. Baker, C.H., Matsuda, S.P., Liu, D.R., Corey, E.J. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  16. Toxicologic lesions associated with two related inhibitors of oxidosqualene cyclase in the dog and mouse. Pyrah, I.T., Kalinowski, A., Jackson, D., Davies, W., Davis, S., Aldridge, A., Greaves, P. Toxicologic pathology. (2001) [Pubmed]
  17. Shear stress regulates gene expression in vascular endothelial cells in response to tumor necrosis factor-alpha: a study of the transcription profile with complementary DNA microarray. Chiu, J.J., Lee, P.L., Chang, S.F., Chen, L.J., Lee, C.I., Lin, K.M., Usami, S., Chien, S. J. Biomed. Sci. (2005) [Pubmed]
  18. Reliability and validity of the Leisure Satisfaction Scale (LSS--short form) and the Adolescent Leisure Interest Profile (ALIP). Trottier, A.N., Brown, G.T., Hobson, S.J., Miller, W. Occupational therapy international. (2002) [Pubmed]
  19. Lumbar epidural steroid injections in the patient with lumbar spinal stenosis. Botwin, K.P., Gruber, R.D. Physical medicine and rehabilitation clinics of North America. (2003) [Pubmed]
  20. Abnormal pulmonary vascular responses in patients registered with a systemic autoimmunity database: Pulmonary Hypertension Assessment and Screening Evaluation using stress echocardiography (PHASE-I). Collins, N., Bastian, B., Quiqueree, L., Jones, C., Morgan, R., Reeves, G. European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology (2006) [Pubmed]
 
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