Abstract
Activation of endoplasmic reticulum (ER) stress-related cell signals has been reported in several neurologic disorders and may contribute to neurodegeneration. Endoplasmic reticulum stress is also linked to ischemic injury. However, activation of an ER stress response has not been investigated in multiple sclerosis (MS) lesions. We detected increased expression of ER stress-associated C/EBP homologous protein, immunoglobulin heavy chain-binding protein, and X-box-binding protein 1 in multiple cell types, including oligodendrocytes, astrocytes, T cells, and microglia in active MS lesions. Semiquantitative analysis of expression in active, chronic active, and chronic inactive lesions indicated that levels of immunoglobulin heavy chain-binding protein were significantly higher in acute lesions than in non-MS controls or MS normal-appearing white matter, and that ER stress-associated C/EBP homologous protein was upregulated to the greatest extent at the edges of chronic active lesions. Because demyelination may be triggered by a tissue response to ischemia-like conditions, changes in the hypoxia-related antigen D-110 were also investigated, and it was found that increased ER stress-associated C/EBP homologous protein expression can occur in either the presence or absence of D-110. A possible link between a perturbed ER and lesion development in MS suggests a signaling pathway that may represent a new therapeutic target in MS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Autoantigens / analysis
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Autoantigens / metabolism
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Biomarkers / analysis
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Biomarkers / metabolism
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Central Nervous System / metabolism*
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Central Nervous System / pathology
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DNA-Binding Proteins / analysis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Endoplasmic Reticulum / metabolism*
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Endoplasmic Reticulum Chaperone BiP
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Female
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Fluorescent Antibody Technique
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Heat-Shock Proteins / analysis
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Heat-Shock Proteins / genetics
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Heat-Shock Proteins / metabolism
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Humans
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Hypoxia / diagnosis
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Hypoxia / metabolism
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Hypoxia / physiopathology
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Male
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Middle Aged
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Molecular Chaperones / analysis
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism
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Multiple Sclerosis / metabolism*
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Multiple Sclerosis / pathology
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Neuroglia / metabolism
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Neuroglia / pathology
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Nuclear Proteins / analysis
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Oxidative Stress*
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Predictive Value of Tests
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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Regulatory Factor X Transcription Factors
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Signal Transduction*
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Transcription Factor CHOP / metabolism*
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Transcription Factors
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Up-Regulation
Substances
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Autoantigens
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Biomarkers
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DNA-Binding Proteins
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Endoplasmic Reticulum Chaperone BiP
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Heat-Shock Proteins
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Molecular Chaperones
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Nuclear Proteins
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RNA, Messenger
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Regulatory Factor X Transcription Factors
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Transcription Factors
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Transcription Factor CHOP