Involvement of IRE1α signaling in the hippocampus in patients with mesial temporal lobe epilepsy

Autor: Gonglu Liu, Hui Guo, Shengjie Zhao, Deshan Gong, Yongbo Zhao, Chunni Guo
Rok vydání: 2011
Předmět:
Adult
Male
X-Box Binding Protein 1
medicine.medical_specialty
Programmed cell death
XBP1
Adolescent
Apoptosis
Regulatory Factor X Transcription Factors
Protein Serine-Threonine Kinases
Biology
Endoplasmic Reticulum
MAP Kinase Kinase Kinase 5
Hippocampus
Young Adult
Downregulation and upregulation
Stress
Physiological
Internal medicine
Endoribonucleases
medicine
Animals
Humans
ASK1
Child
Endoplasmic Reticulum Chaperone BiP
Transcription factor
Heat-Shock Proteins
Hippocampal sclerosis
Membrane Glycoproteins
General Neuroscience
JNK Mitogen-Activated Protein Kinases
TNF Receptor-Associated Factor 2
medicine.disease
Caspases
Initiator
nervous system diseases
DNA-Binding Proteins
Enzyme Activation
Endocrinology
Epilepsy
Temporal Lobe
Unfolded protein response
Cancer research
Female
Signal transduction
Signal Transduction
Transcription Factors
Zdroj: Brain Research Bulletin. 84:94-102
ISSN: 0361-9230
Popis: Cumulative evidence suggests that programmed cell death (apoptosis) may contribute to the progressive hippocampal sclerosis seen in patients with refractory mesial temporal lobe epilepsy (MTLE). The endoplasmic reticulum (ER) stress-mediated cell apoptotic pathway has recently emerged as a vital intrinsic pathway, but the molecular mechanisms underlying this process in the epileptic brain remain unclear. We investigated inositol-requiring protein 1α (IRE1α)-mediated ER stress pro-and anti-apoptotic signaling pathways in resected hippocampi from 32 patients with intractable MTLE. Immunoreactivity for the ER stress markers glucose-regulated proteins 78 and 94 was significantly higher in MTLE hippocampi than in controls. The levels of IRE1α, tumor necrosis factor receptor associated factor 2 (TRAF2), apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK), which together constitute the IRE1α/TRAF2/ASK1/JNK pro-apoptotic signaling pathway, were significantly upregulated in patients with MTLE. Immunoreactivity for caspase-4, a homologue of caspase-12 that is possibly activated by IRE1α via TRAF2 following ER stress, and caspase-3 which was a downstream effector of caspase-4, were both detected in MTLE tissue samples. In contrast, immunoreactivity for caspase-4 and caspase-3 were low or absent in control samples. Simultaneously, the X-box binding protein 1 (XBP1), a basic leucine zipper (bZIP) family transcription factor downstream of IRE1α which can promote cell survival by upregulation of multiple ER-targeted genes, was also overexpressed and activated in MTLE hippocampi. Our data suggest that chronic epilepsy is associated with ER stress, as well as induction of both IRE1α-mediated pro- and anti-apoptotic signaling pathways.
Databáze: OpenAIRE
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