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Open Access Research article

A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells

Raffaella Calligaris12, Cristina Bellarosa34, Rossana Foti1, Paola Roncaglia12, Pablo Giraudi34, Helena Krmac12, Claudio Tiribelli34 and Stefano Gustincich12*

Author Affiliations

1 International School for Advanced Studies (SISSA), Sector of Neurobiology, AREA Science Park, SS 14, Km 163 5, Basovizza, 34012 Trieste, Italy

2 The Giovanni Armenise-Harvard Foundation Laboratory, SS 14, Km 163 5, Basovizza, 34012 Trieste, Italy

3 Centro Studi Fegato, AREA Science Park, SS 14, Km 163 5, Basovizza, 34012 Trieste, Italy

4 Universita' degli Studi di Trieste, 34012 Trieste, Italy

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BMC Genomics 2009, 10:543  doi:10.1186/1471-2164-10-543

Published: 19 November 2009

Abstract

Background

The deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions in other tissues, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown.

Results

Transcriptome changes induced by UCB exposure in SH-SY5Y neuroblastoma cell line were examined by high density oligonucleotide microarrays. Two-hundred and thirty genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that at least 50 genes were directly involved in the endoplasmic reticulum (ER) stress response. Validation of selected ER stress genes is shown by quantitative RT-PCR. Analysis of XBP1 splicing and DDIT3/CHOP subcellular localization is presented.

Conclusion

These results show for the first time that UCB exposure induces ER stress response as major intracellular homeostasis in surviving neuroblastoma cells in vitro.