Identification and classification of genes regulated by phosphatidylinositol 3-kinase- and TRKB-mediated signalling pathways during neuronal differentiation in two subtypes of the human neuroblastoma cell line SH-SY5YReportar como inadecuado




Identification and classification of genes regulated by phosphatidylinositol 3-kinase- and TRKB-mediated signalling pathways during neuronal differentiation in two subtypes of the human neuroblastoma cell line SH-SY5Y - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Research Notes

, 1:95

First Online: 28 October 2008Received: 12 September 2008Accepted: 28 October 2008DOI: 10.1186-1756-0500-1-95

Cite this article as: Nishida, Y., Adati, N., Ozawa, R. et al. BMC Res Notes 2008 1: 95. doi:10.1186-1756-0500-1-95

Abstract

BackgroundSH-SY5Y cells exhibit a neuronal phenotype when treated with all-trans retinoic acid RA, but the molecular mechanism of activation in the signalling pathway mediated by phosphatidylinositol 3-kinase PI3K is unclear. To investigate this mechanism, we compared the gene expression profiles in SK-N-SH cells and two subtypes of SH-SY5Y cells SH-SY5Y-A and SH-SY5Y-E, each of which show a different phenotype during RA-mediated differentiation.

FindingsSH-SY5Y-A cells differentiated in the presence of RA, whereas RA-treated SH-SY5Y-E cells required additional treatment with brain-derived neurotrophic factor BDNF for full differentiation. After exposing cells to a PI3K inhibitor, LY294002, we identified 386 genes and categorised these genes into two clusters dependent on the PI3K signalling pathway during RA-mediated differentiation in SH-SY5Y-A cells. Transcriptional regulation of the gene cluster, including 158 neural genes, was greatly reduced in SK-N-SH cells and partially impaired in SH-SY5Y-E cells, which is consistent with a defect in the neuronal phenotype of these cells. Additional stimulation with BDNF induced a set of neural genes that were down-regulated in RA-treated SH-SY5Y-E cells but were abundant in differentiated SH-SY5Y-A cells.

ConclusionWe identified gene clusters controlled by PI3K- and TRKB-mediated signalling pathways during the differentiation of two subtypes of SH-SY5Y cells. The TRKB-mediated bypass pathway compensates for impaired neural function generated by defects in several signalling pathways, including PI3K in SH-SY5Y-E cells. Our expression profiling data will be useful for further elucidation of the signal transduction-transcriptional network involving PI3K or TRKB.

AbbreviationsRAall-trans retinoic acid

PI3Kphosphatidylinositol 3-kinase

BDNFbrain-derived neurotrophic factor

TRKA NTRK1Tropomyosin-related kinase A

TRKB NTRK2Tropomyosin-related kinase B

MAPKmitogen-activated protein kinase

NT-4-5neurotrophin-4-5

ATCCAmerican Type Culture Collection

ECACCEuropean Collection of Cell Cultures

D-MEM-F12Dulbecco-s modified Eagle-s medium-nutrient mixture F12

FBSFetal Bovine Serum

ANOVAanalysis of variance.

Electronic supplementary materialThe online version of this article doi:10.1186-1756-0500-1-95 contains supplementary material, which is available to authorized users.

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Autor: Yuichiro Nishida - Naoki Adati - Ritsuko Ozawa - Aasami Maeda - Yoshiyuki Sakaki - Tadayuki Takeda

Fuente: https://link.springer.com/







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