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Epigenetic modifications in cell lines of human astrocytoma differentially regulate expression of apoptotic genes

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Abstract

Objects

Epigenetic alterations, known as epimutations, act by deregulating gene expression. These epimutations are reversible through the action of chromatin modifiers such as DNA methylation (DNA-met) and histone deacetylases (HDAC) inhibitors. The present study evaluated the effect of 5-azacitidine (5-aza) and sodium butyrate (NaBu) as inhibitors of DNA-met and HDAC, respectively, in the expression of genes involved in apoptosis.

Methods

D54-MG, U373-MG, and T98G cell lines were exposed to 8 mM of NaBu and 12 μM of 5-aza, as well as a combination of both, for 24 h. The expression of the Bcl-2, Bak-1, Bax, Caspase-3, and Caspase-9 genes was assessed by RT-PCR.

Results

They show that the Bcl-2, Caspase-3, and Caspase-9 genes were not expressed by the U373-MG and T98G lines, and that the D54-MG line did not express Bak-1. After treatment, however, these cell lines expressed all of the genes due to the effect of 5-aza on Bak-1 in D54-MG and Caspase-9 in T98G, which suggests repression by DNA-met. Meanwhile, Bcl-2, Caspase-3, and Caspase-9 were in the U373-MG and T98G lines expressed after NaBu treatment. The effect of 5-aza induced an increase in the expression of Bax and Bcl-2, while NaBu produced a similar effect on the Bak-1 and Bax genes.

Conclusions

Results reveal that histone deacetylation is the principle mechanism for repressing these genes and that their basal expression is regulated primarily by this form of histone modification.

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Acknowledgments

The authors thank the Dirección de Investigación at the Hospital Infantil de México Federico Gómez for its support (HIM/2007/020); as well as Mexico’s National Science and Technology Council (CONACyT), through FOSISS SALUD-2012-01-181456; and Sistema Nacional de Investigadores (SNI) (Francisco Arenas-Huertero).

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Authors and Affiliations

  1. Departamento de Patología, Hospital Infantil de México Federico Gómez, Mexico City, Mexico

    Mario Solís-Paredes, Pilar Eguía-Aguilar, Stanislaw Sadowinski-Pine, Mario Pérezpeña-Diazconti & Francisco Arenas-Huertero

  2. Departamento de Neurocirugía, Hospital Infantil de México Federico Gómez, Mexico City, Mexico

    Fernando Chico-Ponce de León

  3. Laboratorio de Patología Molecular, Hospital Infantil de México Federico Gómez, Avenida Dr. Márquez 162. Colonia Doctores, 06720, Mexico, D. F., Mexico

    Francisco Arenas-Huertero

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  1. Mario Solís-Paredes
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  2. Pilar Eguía-Aguilar
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  3. Fernando Chico-Ponce de León
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  4. Stanislaw Sadowinski-Pine
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  5. Mario Pérezpeña-Diazconti
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  6. Francisco Arenas-Huertero
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Correspondence to Francisco Arenas-Huertero.

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Solís-Paredes, M., Eguía-Aguilar, P., Chico-Ponce de León, F. et al. Epigenetic modifications in cell lines of human astrocytoma differentially regulate expression of apoptotic genes. Childs Nerv Syst 30, 123–129 (2014). https://doi.org/10.1007/s00381-013-2258-6

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  • DOI: https://doi.org/10.1007/s00381-013-2258-6

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