Peer Reviewed

1

Document Type

Article

Publication Date

12-2014

Keywords

CHOP, epilepsy, mRNA microarray, myelin basic protein, status epilepticus

Funder/Sponsor

Health Research Board. Science Foundation Ireland.

Comments

The original article is available at http://www.ijppp.org/

Abstract

The C/EBP homologous protein CHOP is normally present at low levels in cells but increases rapidly after insults such as DNA damage or endoplasmatic reticulum stress where it contributes to cellular homeostasis and apoptosis. By forming heterodimers with other transcription factors, CHOP can either act as a dominant-negative regulator of gene expression or to induce the expression of target genes. Recent work demonstrated that seizure-induced hippocampal damage is significantly worse in mice lacking CHOP and these animals go on to develop an aggravated epileptic phenotype. To identify novel CHOP-controlled target genes which potentially influence the epileptic phenotype, we performed a bioinformatics analysis of tissue microarrays from chop-deficient mice after prolonged seizures. GO analysis revealed genes associated with biological membranes were prominent among those in the chop-deficient array dataset and we identified myelin-associated genes to be particularly de-repressed. These data suggest CHOP might act as an inhibitor of myelin-associated processes in the brain and could be targeted to influence axonal regeneration or reorganisation.

Disciplines

Physics | Physiology

Citation

Sheedy C, Mooney C, Jimenez-Mateos E, Sanz-Rodriguez A, Langa E, Mooney C, Engel T. De-repression of myelin-regulating gene expression after status epilepticus in mice lacking the C/EBP homologous protein CHOP. International Journal of Physiology, Pathophysiology and Pharmacology. 2014;6(4):185-98

PubMed ID

25755840

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