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Abstract:

Several studies indicate that hyaluronan oligosaccharides (oHA) are able to modulate growth and cell survival in solid tumors; however, no studies have been undertaken to analyze the effect of oHA on T-lymphoid disorders. In this work we showed that oHA were able to induce apoptosis in lymphoma cell lines. Since PI3-K/Akt and nuclear factor-κB (NF-κB) are major factors involved in cell survival and anti-apoptotic pathways in lymphoma cells, we hypothesized that oHA could induce apoptosis through inhibition of these pathways. oHA were identified by a method which allows characterization of length using a high pH anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). oHA inhibited PIP3 production (principal product of PI3-K activity) and reduced Akt phosphorylation levels, similarly to the specific inhibitor wortmannin. However, treatment with either oHA or wortmannin failed to inhibit constitutive NF-κB activity and modulate IκBα protein levels, suggesting that PI3-K and NF-κB signaling pathways are not related in the cell lines used. Cell behavior differed using native hyaluronan (HA), which induced PIP3 production, Akt phosphorylation, and NF-κB activation, although not related with cell survival since treatment with native HA showed no effect on apoptosis. Our results suggest that oHA induce apoptosis by suppression of PI3-K/Akt cell survival pathway without involving NF-κB activation, through a mechanism that differs from the one mediated by native HA. © 2006 Oxford University Press.

Registro:

Documento: Artículo
Título:Hyaluronan oligosaccharides induce cell death through PI3-K/Akt pathway independently of NF-κB transcription factor
Autor:Alaniz, L.; García, M.G.; Gallo-Rodriguez, C.; Agusti, R.; Sterín-Speziale, N.; Hajos, S.E.; Alvarez, E.
Filiación:Cátedra de Inmunología-IDEHU, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica, UBA, Buenos Aires, Argentina
Palabras clave:Akt; Apoptosis; HPAEC-PAD; Hyaluronan oligomers; NF-κB; P13-K; hyaluronic acid; I kappa B alpha; immunoglobulin enhancer binding protein; oligosaccharide; phosphatidylinositol 3 kinase; phosphatidylinositol 3,4,5 trisphosphate; protein kinase B; wortmannin; amperometry; animal cell; anion exchange chromatography; apoptosis; article; cancer cell culture; cell death; cell function; cell survival; controlled study; enzyme activity; enzyme inhibition; enzyme synthesis; hypothesis; inhibition kinetics; lymphoma; mouse; nonhuman; pH; priority journal; protein phosphorylation; signal transduction; 1-Phosphatidylinositol 3-Kinase; Animals; Apoptosis; Cell Death; Cell Line, Tumor; Dose-Response Relationship, Drug; Hyaluronic Acid; Lymphoma; Mice; Molecular Weight; NF-kappa B; Proto-Oncogene Proteins c-akt; Signal Transduction; Animalia
Año:2006
Volumen:16
Número:5
Página de inicio:359
Página de fin:367
DOI: http://dx.doi.org/10.1093/glycob/cwj085
Título revista:Glycobiology
Título revista abreviado:Glycobiology
ISSN:09596658
CODEN:GLYCE
CAS:hyaluronic acid, 31799-91-4, 9004-61-9, 9067-32-7; I kappa B alpha, 151217-48-0; phosphatidylinositol 3 kinase, 115926-52-8; protein kinase B, 148640-14-6; wortmannin, 19545-26-7; 1-Phosphatidylinositol 3-Kinase, EC 2.7.1.137; Hyaluronic Acid, 9004-61-9; NF-kappa B; Proto-Oncogene Proteins c-akt, EC 2.7.1.37
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_09596658_v16_n5_p359_Alaniz.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09596658_v16_n5_p359_Alaniz

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Citas:

---------- APA ----------
Alaniz, L., García, M.G., Gallo-Rodriguez, C., Agusti, R., Sterín-Speziale, N., Hajos, S.E. & Alvarez, E. (2006) . Hyaluronan oligosaccharides induce cell death through PI3-K/Akt pathway independently of NF-κB transcription factor. Glycobiology, 16(5), 359-367.
http://dx.doi.org/10.1093/glycob/cwj085
---------- CHICAGO ----------
Alaniz, L., García, M.G., Gallo-Rodriguez, C., Agusti, R., Sterín-Speziale, N., Hajos, S.E., et al. "Hyaluronan oligosaccharides induce cell death through PI3-K/Akt pathway independently of NF-κB transcription factor" . Glycobiology 16, no. 5 (2006) : 359-367.
http://dx.doi.org/10.1093/glycob/cwj085
---------- MLA ----------
Alaniz, L., García, M.G., Gallo-Rodriguez, C., Agusti, R., Sterín-Speziale, N., Hajos, S.E., et al. "Hyaluronan oligosaccharides induce cell death through PI3-K/Akt pathway independently of NF-κB transcription factor" . Glycobiology, vol. 16, no. 5, 2006, pp. 359-367.
http://dx.doi.org/10.1093/glycob/cwj085
---------- VANCOUVER ----------
Alaniz, L., García, M.G., Gallo-Rodriguez, C., Agusti, R., Sterín-Speziale, N., Hajos, S.E., et al. Hyaluronan oligosaccharides induce cell death through PI3-K/Akt pathway independently of NF-κB transcription factor. Glycobiology. 2006;16(5):359-367.
http://dx.doi.org/10.1093/glycob/cwj085