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SIGMAR1  -  sigma non-opioid intracellular receptor 1

Homo sapiens

Synonyms: AAG8, ALS16, Aging-associated gene 8 protein, OPRS1, SIG-1R, ...
 
 
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Disease relevance of OPRS1

  • Immunohistochemical studies detected the sigma receptor 1 protein in retinal ganglion, photoreceptor, RPE cells and surrounding the soma of cells in the inner nuclear layer [1].
  • The demonstration that sigma receptor 1 is present in ganglion cells is particularly noteworthy given the well-documented susceptibility of these cells to glutamate toxicity [1].
  • Twenty patients (group B, 48%) had a distinct new increase of Q waves (delta sigma Q = 3.0 +/- 2.0 mV/hours) and further R-wave reduction (-delta sigma R = 1.0 +/- 0.6 mV/hour) simultaneous with new severe chest pain and a delayed second increase of enzyme release corresponding with extension of infarction [2].
  • In a large group of patients evaluated for chest pain, we examined the relationship between the arithmetic summation of RX + RY + QZ (sigma R), the maximal and mean spatial QRS vectors and the ejection fraction (EF) [3].
  • In the group with myocardial infarction, a significant correlation between sigma R and EF existed only in patients with anterior myocardial infarction (r:0.41, P less than 0.025) [3].
 

Psychiatry related information on OPRS1

  • The OPRS complements traditional evaluations by providing objective assessment of operative decision-making and technical skills [4].
  • The findings also show that DSV Oprs prefer to take fewer risks than divers, while the DSV Crs are more like divers in risk-taking behavior [5].
 

High impact information on OPRS1

  • Diastolic active left ventricular pressure decay, extrapolated from the exponential fit, was subtracted from the measured left ventricular pressure (which is equal in magnitude but opposite in sign to the radial stress at the endocardium) to calculate residual left ventricular pressure (PR) and hence residual stress (sigma R = -PR) [6].
  • Using a radiolabeled chemical probe, we here purified a target of SR 31747A and called it SR 31747A-binding protein (SR-BP) [7].
  • Cloning of the cDNA encoding human SR-BP shows an open reading frame for a 223-amino acid protein, which is homologous to the recently cloned sigma 1 receptor [7].
  • Subcellular localization analysis in various cells, using a specific monoclonal antibody raised against SR-BP, demonstrated that this protein was associated with the nuclear envelope [7].
  • Taken together, these findings strongly suggest that SR-BP represents the molecular target for SR 31747A in mammalian tissues, which could be critical for T cell proliferation [7].
 

Chemical compound and disease context of OPRS1

 

Biological context of OPRS1

  • CONCLUSION: The present study suggests that the TT-241-240P2 haplotype of the SIGMAR1 gene, which decreases expression of the gene, may have a protective role against susceptibility to AD [9].
  • Northern blot analysis of SR-BP gene expression revealed a single transcript of 2 kilobases which was widely expressed among organs, with the highest abundance in liver and the lowest abundance in brain [7].
  • Sigma receptor antagonists inhibit human lens cell growth and induce pigmentation [10].
  • Sigma receptor ligands protect human retinal cells against oxidative stress [11].
  • The ITA provides three convenient biomechanical parameters--peak stress (sigma p), stress relaxation (sigma R), and diffusion coefficient (D)--to quantify the kinetics of swelling [12].
 

Anatomical context of OPRS1

 

Associations of OPRS1 with chemical compounds

  • Sigma receptor is a protein that interacts with a variety of psychotomimetic drugs including cocaine and amphetamines and is believed to play an important role in the cellular functions of various tissues associated with the endocrine, immune, and nervous systems [16].
  • Two SR31747A targets were recently identified and termed sigma(1) or SR-BP-1 (SR31747A-binding protein-1) and hSI (human sterol isomerase) [17].
  • The resultant bags were cultured in Eagle's minimum essential medium (EMEM) alone or supplemented with the Sigma receptor antagonists rimcazole (3 microM) and BD1047 (10 microM) [10].
  • Three mixing indexes (s/sigma A, s/sigma R, and the Ashton-Valentin mixing index) were used to evaluate mixing of the three drugs with lactose [18].
  • The effect of three different fixation methods, RNAlater (SIGMA R 0901, St Louis, MO), acetone, and formalin, were compared by histology, immunohistochemistry, and real-time PCR [19].
 

Regulatory relationships of OPRS1

  • Anti-IP3R-3 immunoprecipitates from cells expressing sigma-1R or C-fragment contained significantly less ANK 220 compared with untransfected or N-fragment cells, indicating a higher amount of ankyrin-free IP3R-3 [20].
 

Other interactions of OPRS1

  • After stratification by epsilon4 allele status of the apolipoprotein E gene, TT-241-240P2 homozygosity of the SIGMAR1 gene reduced the risk of AD in epsilon4 allele carriers by three-fourths [9].
  • Indeed, while competitive experiments indicated that EBP prevails in mediating SR31747A antiproliferative activity, an analysis of the expression of both receptors indicated that the cellular sensitivity to SR31747A is not correlated with either EBP or SR-BP expression [21].
 

Analytical, diagnostic and therapeutic context of OPRS1

  • Reverse transcription-polymerase chain reaction (RT-PCR) analysis amplified sigma receptor 1 in neural retina, RPE-choroid complex, and lens isolated from mice [1].
  • In situ hybridization analysis revealed abundant sigma receptor 1 expression in ganglion cells, cells of the inner nuclear layer, inner segments of photoreceptor cells and retinal pigment epithelial (RPE) cells [1].
  • Also, the third index, that is, the ECG, showed a favorable trend toward a lesser number of Q waves and a higher sigma R waves, although the values did not reach statistical significance [22].
  • To investigate the role of SIGMAR1 in conveying susceptibility to alcoholism, we performed a functional analysis of polymorphisms in the SIGMAR1 and a case-control study [23].
  • Sigma receptor scintigraphy with N-[2-(1'-piperidinyl)ethyl]-3-(123)I-iodo-4-methoxybenzamide of patients with suspected primary breast cancer: first clinical results [24].

References

  1. Expression pattern of sigma receptor 1 mRNA and protein in mammalian retina. Ola, M.S., Moore, P., El-Sherbeny, A., Roon, P., Agarwal, N., Sarthy, V.P., Casellas, P., Ganapathy, V., Smith, S.B. Brain Res. Mol. Brain Res. (2001) [Pubmed]
  2. QRS mapping in the evaluation of acute anterior myocardial infarction. von Essen, R., Merx, W., Doerr, R., Effert, S., Silny, J., Rau, G. Circulation (1980) [Pubmed]
  3. Reassessment of the relation between QRS forces of the orthogonal electrocardiogram and left ventricular ejection fraction. Luwaert, R.J., Cosyns, J., Rousseau, M.F., Brasseur, L.A., Detry, J.M., Brohet, C.R. Eur. Heart J. (1983) [Pubmed]
  4. Feasibility, reliability and validity of an operative performance rating system for evaluating surgery residents. Larson, J.L., Williams, R.G., Ketchum, J., Boehler, M.L., Dunnington, G.L. Surgery (2005) [Pubmed]
  5. Psychological characteristics of deep submergence vehicle personnel. Biersner, R.J., Hall, D.A., Linaweaver, P.G. Aviation, space, and environmental medicine. (1975) [Pubmed]
  6. Increased regional myocardial stiffness of the left ventricle during pacing-induced angina in man. Bourdillon, P.D., Lorell, B.H., Mirsky, I., Paulus, W.J., Wynne, J., Grossman, W. Circulation (1983) [Pubmed]
  7. Purification and characterization of the human SR 31747A-binding protein. A nuclear membrane protein related to yeast sterol isomerase. Jbilo, O., Vidal, H., Paul, R., De Nys, N., Bensaid, M., Silve, S., Carayon, P., Davi, D., Galiègue, S., Bourrié, B., Guillemot, J.C., Ferrara, P., Loison, G., Maffrand, J.P., Le Fur, G., Casellas, P. J. Biol. Chem. (1997) [Pubmed]
  8. Sigma receptor-active neuroleptics are cytotoxic to C6 glioma cells in culture. Vilner, B.J., Bowen, W.D. Eur. J. Pharmacol. (1993) [Pubmed]
  9. A variant of the sigma receptor type-1 gene is a protective factor for Alzheimer disease. Uchida, N., Ujike, H., Tanaka, Y., Sakai, A., Yamamoto, M., Fujisawa, Y., Kanzaki, A., Kuroda, S. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. (2005) [Pubmed]
  10. Sigma receptor antagonists inhibit human lens cell growth and induce pigmentation. Wang, L., Prescott, A.R., Spruce, B.A., Sanderson, J., Duncan, G. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  11. Sigma receptor ligands protect human retinal cells against oxidative stress. Bucolo, C., Drago, F., Lin, L.R., Reddy, V.N. Neuroreport (2006) [Pubmed]
  12. Tensile properties of human knee joint cartilage. II. Correlations between weight bearing and tissue pathology and the kinetics of swelling. Akizuki, S., Mow, V.C., Muller, F., Pita, J.C., Howell, D.S. J. Orthop. Res. (1987) [Pubmed]
  13. Molecular and ligand-binding characterization of the sigma-receptor in the Jurkat human T lymphocyte cell line. Ganapathy, M.E., Prasad, P.D., Huang, W., Seth, P., Leibach, F.H., Ganapathy, V. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  14. sigma Receptor ligand-induced up-regulation of the H(+)/peptide transporter PEPT1 in the human intestinal cell line Caco-2. Fujita, T., Majikawa, Y., Umehisa, S., Okada, N., Yamamoto, A., Ganapathy, V., Leibach, F.H. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  15. Sigma receptor activation reduces infarct size at 24 hours after permanent middle cerebral artery occlusion in rats. Ajmo, C.T., Vernon, D.O., Collier, L., Pennypacker, K.R., Cuevas, J. Current neurovascular research. (2006) [Pubmed]
  16. Exon-intron structure, analysis of promoter region, and chromosomal localization of the human type 1 sigma receptor gene. Prasad, P.D., Li, H.W., Fei, Y.J., Ganapathy, M.E., Fujita, T., Plumley, L.H., Yang-Feng, T.L., Leibach, F.H., Ganapathy, V. J. Neurochem. (1998) [Pubmed]
  17. Colocalization of sterol isomerase and sigma(1) receptor at endoplasmic reticulum and nuclear envelope level. Dussossoy, D., Carayon, P., Belugou, S., Feraut, D., Bord, A., Goubet, C., Roque, C., Vidal, H., Combes, T., Loison, G., Casellas, P. Eur. J. Biochem. (1999) [Pubmed]
  18. Mixing of pharmaceutical solids. II: Evaluation of multicomponent mixing of cohesive powders in cylindrical shear mixer. Chowhan, Z.T., Linn, E.E., Chi, L.H. Journal of pharmaceutical sciences. (1981) [Pubmed]
  19. Effect of formalin, acetone, and RNAlater fixatives on tissue preservation and different size amplicons by real-time PCR from paraffin-embedded tissue. Páska, C., Bögi, K., Szilák, L., Tokés, A., Szabó, E., Sziller, I., Rigó, J., Sobel, G., Szabó, I., Kaposi-Novák, P., Kiss, A., Schaff, Z. Diagn. Mol. Pathol. (2004) [Pubmed]
  20. Role of sigma-1 receptor C-terminal segment in inositol 1,4,5-trisphosphate receptor activation: constitutive enhancement of calcium signaling in MCF-7 tumor cells. Wu, Z., Bowen, W.D. J. Biol. Chem. (2008) [Pubmed]
  21. SR31747A is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo. Berthois, Y., Bourrié, B., Galiègue, S., Vidal, H., Carayon, P., Martin, P.M., Casellas, P. Br. J. Cancer (2003) [Pubmed]
  22. Prodromal angina limits infarct size. A role for ischemic preconditioning. Ottani, F., Galvani, M., Ferrini, D., Sorbello, F., Limonetti, P., Pantoli, D., Rusticali, F. Circulation (1995) [Pubmed]
  23. Functional polymorphisms in the sigma1 receptor gene associated with alcoholism. Miyatake, R., Furukawa, A., Matsushita, S., Higuchi, S., Suwaki, H. Biol. Psychiatry (2004) [Pubmed]
  24. Sigma receptor scintigraphy with N-[2-(1'-piperidinyl)ethyl]-3-(123)I-iodo-4-methoxybenzamide of patients with suspected primary breast cancer: first clinical results. Caveliers, V., Everaert, H., John, C.S., Lahoutte, T., Bossuyt, A. J. Nucl. Med. (2002) [Pubmed]
 
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