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

Claire Mooney¹  Elena Langa¹  Tobias Engel¹  Catherine Mooney¹  Caroline Sheedy¹  Eva Jimenez-Mateos¹  Amaya Sanz-Rodriguez¹ 

关键词: CHOP;    epilepsy;    mRNA microarray;    myelin basic protein;    status epilepticus;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

Unknown