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Dansey, M.V.; Alvarez, L.D.; Samaja, G.; Escudero, D.S.; Veleiro, A.S.; Pecci, A.; Castro, O.A.; Burton, G. "Synthetic DAF-12 modulators with potential use in controlling the nematode life cycle" (2015) Biochemical Journal. 465:175-184
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Abstract:

Dafachronic acids (DAs) are 3-keto cholestenoic acids bearing a carboxylic acid moiety at the end of the steroid side chain. These compounds interact with the DAF-12 receptor, a ligand-dependent transcription factor that acts as a molecular switch mediating the choice between arrest at diapause or progression to reproductive development and adult lifespan in different nematodes. Recently, we reported that the 27-nor-Δ4-DA was able to directly activate DAF-12 in a transactivation cell-based luciferase assay and rescued the Mig phenotype of daf-9(rh50) Caenorhabditis elegans mutants. In the present paper, to investigate further the relationship between the structure of the steroid side chain and DAF-12 activity, we evaluated the in vitro and in vivo activity of Δ4-DA analogues with modified side chains using transactivation cell-based assays and daf-9(dh6) C. elegans mutants. Our results revealed that introduction of a 24,25-double bond on the cholestenoic acid side chain did not affect DAF-12 activity, whereas shortening the side chain lowered the activity. Most interestingly, the C24 alcohol 24-hydroxy-4-cholen-3-one (6) was an antagonist of the DAF-12 receptor both in vitro and in vivo. © The Authors Journal compilation © 2015 Biochemical Society.

Registro:

Documento: Artículo
Título:Synthetic DAF-12 modulators with potential use in controlling the nematode life cycle
Autor:Dansey, M.V.; Alvarez, L.D.; Samaja, G.; Escudero, D.S.; Veleiro, A.S.; Pecci, A.; Castro, O.A.; Burton, G.
Filiación:Departamento de Química Biológica and IFIBYNE (CONICET-UBA), Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, Buenos Aires, C1428EGA, Argentina
Departamento de Química Orgánica and UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, Buenos Aires, C1428EGA, Argentina
Departamento de Química Biológica and IQUIBICEN (CONICET-UBA), Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, Buenos Aires, C1428EGA, Argentina
Palabras clave:Caenorhabditis elegans; DAF-12 receptor; Daf-9 mutant; Dafachronic acid; Molecular dynamics; 24 hydroxy 4 cholen 3 one; alcohol derivative; carboxylic acid derivative; dafachronic acid receptor 12; steroid; unclassified drug; Caenorhabditis elegans protein; cell receptor; cholestane derivative; DAF-12 protein, C elegans; dafachronic acid; ligand; animal experiment; Article; biological activity; Caenorhabditis elegans; concentration response; conformation; controlled study; developmental stage; HEK293 cell line; human; human cell; in vitro study; in vivo study; life cycle; luciferase assay; nonhuman; phenotype; quantum chemistry; transactivation; allele; animal; Caenorhabditis elegans; chemistry; drug effects; growth, development and aging; life cycle stage; metabolism; reporter gene; Caenorhabditis elegans; Nematoda; Alleles; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cholestenes; Genes, Reporter; HEK293 Cells; Humans; Life Cycle Stages; Ligands; Receptors, Cytoplasmic and Nuclear
Año:2015
Volumen:465
Página de inicio:175
Página de fin:184
DOI: http://dx.doi.org/10.1042/BJ20140833
Título revista:Biochemical Journal
Título revista abreviado:Biochem. J.
ISSN:02646021
CODEN:BIJOA
CAS:Caenorhabditis elegans Proteins; Cholestenes; DAF-12 protein, C elegans; dafachronic acid; Ligands; Receptors, Cytoplasmic and Nuclear
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02646021_v465_n_p175_Dansey

Referencias:

  • Kenyon, C., A pathway that links reproductive status to lifespan in Caenorhabditis elegans (2010) Ann. N.Y. Acad. Sci., 1204, pp. 156-162. , CrossRef PubMed
  • Kaletta, T., Hengartner, M.O., Finding function in novel targets: C. Elegans as a model organism (2006) Nat. Rev. Drug Discov., 5, pp. 387-398. , CrossRef PubMed
  • Lapierre, L.R., Hansen, M., Lessons from C. Elegans: Signaling pathways for longevity (2012) Trends Endocrinol. Metab., 23, pp. 637-644. , CrossRef PubMed
  • Butcher, R.A., Fujita, M., Schroeder, F.C., Clardy, J., Small-molecule pheromones that control dauer development in Caenorhabditis elegans (2007) Nat. Chem. Biol., 3, pp. 420-422. , CrossRef PubMed
  • Golden, J.W., Riddle, D.L., The Caenorhabditis elegans dauer larva: Developmental effects of pheromone, food, and temperature (1984) Dev. Biol., 102, pp. 368-378. , CrossRef PubMed
  • Cassada, R.C., Russell, R.L., The dauerlarva, a post-embryonic developmental variant of the nematode Caenorhabditis elegans (1975) Dev. Biol., 46, pp. 326-342. , CrossRef PubMed
  • Fielenbach, N., Antebi, A., C. Elegans dauer formation and the molecular basis of plasticity (2008) Genes Dev., 22, pp. 2149-2165. , CrossRef PubMed
  • Antebi, A., Steroid regulation of C. Elegans diapause, developmental timing, and longevity (2013) Curr. Top. Dev. Biol., 105, pp. 181-212. , CrossRef PubMed
  • Motola, D.L., Cummins, C.L., Rottiers, V., Sharma, K.K., Li, T., Li, Y., Suino-Powell, K., Mangelsdorf, D.J., Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. Elegans (2006) Cell, 124, pp. 1209-1223. , CrossRef PubMed
  • Mahanti, P., Bose, N., Bethke, A., Judkins, J.C., Wollam, J., Dumas, K.J., Zimmerman, A.M., Schroeder, F.C., Comparative metabolomics reveals endogenous ligands of DAF-12, a nuclear hormone receptor, regulating C. Elegans development and lifespan (2014) Cell Metab., 19, pp. 73-83. , CrossRef PubMed
  • Shen, Y., Wollam, J., Magner, D., Karalay, O., Antebi, A., A steroid receptor-microRNA switch regulates life span in response to signals from the gonad (2012) Science, 338, pp. 1472-1476. , CrossRef PubMed
  • Schaedel, O.N., Gerisch, B., Antebi, A., Sternberg, P.W., Hormonal signal amplification mediates environmental conditions during development and controls an irreversible commitment to adulthood (2012) PLoS Biol., 10, p. e1001306. , CrossRef PubMed
  • Hochbaum, D., Zhang, Y., Stuckenholz, C., Labhart, P., Alexiadis, V., Martin, R., Knolker, H.J., Fisher, A.L., DAF-12 regulates a connected network of genes to ensure robust developmental decisions (2011) PLoS Genet., 7, p. e1002179. , CrossRef PubMed
  • Ludewig, A.H., Kober-Eisermann, C., Weitzel, C., Bethke, A., Neubert, K., Gerisch, B., Hutter, H., Antebi, A., A novel nuclear receptor/coregulator complex controls C. Elegans lipid metabolism, larval development, and aging (2004) Genes Dev., 18, pp. 2120-2133. , CrossRef PubMed
  • Wollam, J., Magner, D.B., Magomedova, L., Rass, E., Shen, Y., Rottiers, V., Habermann, B., Antebi, A., A novel 3-hydroxysteroid dehydrogenase that regulates reproductive development and longevity (2012) PLoS Biol., 10, p. e1001305. , CrossRef PubMed
  • Gerisch, B., Weitzel, C., Kober-Eisermann, C., Rottiers, V., Antebi, A., A hormonal signaling pathway influencing C. Elegans metabolism, reproductive development, and life span (2001) Dev. Cell, 1, pp. 841-851. , CrossRef PubMed
  • Jia, K., Albert, P.S., Riddle, D.L., DAF-9, a cytochrome P450 regulating C. Elegans larval development and adult longevity (2002) Development, 129, pp. 221-231. , PubMed
  • Martin, R., Entchev, E.V., Kurzchalia, T.V., Knolker, H.J., Steroid hormones controlling the life cycle of the nematode Caenorhabditis elegans: Stereoselective synthesis and biology (2010) Org. Biomol. Chem., 8, pp. 739-750. , CrossRef PubMed
  • Alvarez, L.D., Arroyo Manez, P., Estrin, D.A., Burton, G., The Caenorhabditis elegans DAF-12 nuclear receptor: Structure, dynamics, and interaction with ligands (2012) Proteins, 80, pp. 1798-1809. , PubMed
  • Samaja, G.A., Castro, O., Alvarez, L.D., Dansey, M.V., Escudero, D.S., Veleiro, A.S., Pecci, A., Burton, G., 27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor (2013) Bioorg. Med. Chem. Lett., 23, pp. 2893-2896. , CrossRef PubMed
  • Gioiello, A., Sabbatini, P., Rosatelli, E., Macchiarulo, A., Pellicciani, R., Divergent and stereoselective synthesis of dafachronic acids (2011) Tetrahedron, 67, pp. 1924-1929. , CrossRef
  • Cheatham, T.E., III, Cieplak, P., Kollman, P.A., A modified version of the Cornell et al. Force field with improved sugar pucker phases and helical repeat (1999) J. Biomol. Struct. Dyn., 16, pp. 845-862. , CrossRef PubMed
  • Berendsen, H.J.C., Postma, J.P.M., Van Gunsteren, W.F., DiNola, A., Haak, J.R., Molecular dynamics with coupling to an external bath (1984) J. Chem. Phys., 81, pp. 3684-3690. , CrossRef
  • Mooijaart, S.P., Kuningas, M., Westendorp, R.G., Houwing-Duistermaat, J.J., Slagboom, P.E., Rensen, P.C., Van Heemst, D., Liver X receptor α associates with human life span (2007) J. Gerontol. A Biol. Sci. Med. Sci., 62, pp. 343-349. , CrossRef PubMed
  • Gerisch, B., Rottiers, V., Li, D., Motola, D.L., Cummins, C.L., Lehrach, H., Mangelsdorf, D.J., Antebi, A., A bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling (2007) Proc. Natl. Acad. Sci. U.S.A., 104, pp. 5014-5019. , CrossRef PubMed
  • Albert, P.S., Riddle, D.L., Developmental alterations in sensory neuroanatomy of the Caenorhabditis elegans dauer larva (1983) J. Comp. Neurol., 219, pp. 461-481. , CrossRef PubMed
  • Gerisch, B., Antebi, A., Hormonal signals produced by DAF-9/cytochrome P450 regulate C. Elegans dauer diapause in response to environmental cues (2004) Development, 131, pp. 1765-1776. , CrossRef PubMed
  • Flocco, M.M., Mowbray, S.L., Planar stacking interactions of arginine and aromatic side-chains in proteins (1994) J. Mol. Biol., 235, pp. 709-717. , CrossRef PubMed
  • Brown, A.J., Slatopolsky, E., Vitamin D analogs: Therapeutic applications and mechanisms for selectivity (2008) Mol. Aspects Med., 29, pp. 433-452. , CrossRef PubMed
  • Singarapu, K.K., Zhu, J., Tonelli, M., Rao, H., Assadi-Porter, F.M., Westler, W.M., DeLuca, H.F., Markley, J.L., Ligand-specific structural changes in the vitamin D receptor in solution (2011) Biochemistry, 50, pp. 11025-11033. , CrossRef PubMed

Citas:

---------- APA ----------
Dansey, M.V., Alvarez, L.D., Samaja, G., Escudero, D.S., Veleiro, A.S., Pecci, A., Castro, O.A.,..., Burton, G. (2015) . Synthetic DAF-12 modulators with potential use in controlling the nematode life cycle. Biochemical Journal, 465, 175-184.
http://dx.doi.org/10.1042/BJ20140833
---------- CHICAGO ----------
Dansey, M.V., Alvarez, L.D., Samaja, G., Escudero, D.S., Veleiro, A.S., Pecci, A., et al. "Synthetic DAF-12 modulators with potential use in controlling the nematode life cycle" . Biochemical Journal 465 (2015) : 175-184.
http://dx.doi.org/10.1042/BJ20140833
---------- MLA ----------
Dansey, M.V., Alvarez, L.D., Samaja, G., Escudero, D.S., Veleiro, A.S., Pecci, A., et al. "Synthetic DAF-12 modulators with potential use in controlling the nematode life cycle" . Biochemical Journal, vol. 465, 2015, pp. 175-184.
http://dx.doi.org/10.1042/BJ20140833
---------- VANCOUVER ----------
Dansey, M.V., Alvarez, L.D., Samaja, G., Escudero, D.S., Veleiro, A.S., Pecci, A., et al. Synthetic DAF-12 modulators with potential use in controlling the nematode life cycle. Biochem. J. 2015;465:175-184.
http://dx.doi.org/10.1042/BJ20140833