ArticleActa neuropathologica communications2013
Calreticulin and other components of endoplasmic reticulum stress in rat and human inflammatory demyelination.
Article in Acta neuropathologica communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 60 citations in OpenAlex.
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- The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis.Scientific reports · 2025Article
- SorCS2 Is Important for Astrocytic Function in Neurovascular Signaling.Acta physiologica (Oxford, England) · 2025Article
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- Calreticulin-From the Endoplasmic Reticulum to the Plasma Membrane-Adventures of a Wandering Protein.Cancers · 2025Review
- Annexin A1, calreticulin and high mobility group box 1 are elevated in secondary progressive multiple sclerosis: Does immunogenic cell death occur in multiple sclerosis?BioImpacts : BI · 2025Article
- Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression.Nature communications · 2024Article
- Complete Freund's adjuvant as a confounding factor in multiple sclerosis research.Frontiers in immunology · 2024Review
- Opposite modulation of functional recovery following contusive spinal cord injury in mice with oligodendrocyte-selective deletions of Atf4 and Chop/Ddit3.Scientific reports · 2023Article
- Immunomodulatory therapy with glatiramer acetate reduces endoplasmic reticulum stress and mitochondrial dysfunction in experimental autoimmune encephalomyelitis.Scientific reports · 2023Article
- Endoplasmic Reticulum Stress-Regulated Chaperones as a Serum Biomarker Panel for Parkinson's Disease.Molecular neurobiology · 2023Article
- Oxygen treatment reduces neurological deficits and demyelination in two animal models of multiple sclerosis.Neuropathology and applied neurobiology · 2023Article
- The many faces of parasite calreticulin.Frontiers in immunology · 2023Review
- Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations inBiomolecules · 2022Article
- Endoplasmic reticulum stress as a key mechanism in stunted growth of seawater rainbow trout (Oncorhynchus mykiss).BMC genomics · 2021Article
- The Unfolded Protein Response in Immune Cells as an Emerging Regulator of Neuroinflammation.Frontiers in aging neuroscience · 2021Article
- Endoplasmic Reticulum Stress-Associated Neuronal Death and Innate Immune Response in Neurological Diseases.Frontiers in immunology · 2021Review
- Unfolded protein response in myelin disorders.Neural regeneration research · 2020Review
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7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCalreticulin (CRT) is a chaperone protein, which aids correct folding of glycosylated proteins in the endoplasmic reticulum (ER). Under conditions of ER stress, CRT is upregulated and may be displayed on the surface of cells or be secreted. This 'ecto-CRT' may activate the innate immune response or it may aid clearance of apoptotic cells. Our and other studies have demonstrated upregulation of ER stress markers CHOP, BiP, ATF4, XBP1 and phosphorylated e-IF2 alpha (p-eIF2 alpha) in biopsy and post-mortem human multiple sclerosis (MS) samples. We extend this work by analysing changes in expression of CRT, BiP, CHOP, XBP1 and p-eIF2 alpha in a rat model of inflammatory demyelination. Demyelination was induced in the spinal cord by intradermal injection of recombinant mouse MOG mixed with incomplete Freund's adjuvant (IFA) at the base of the tail. Tissue samples were analysed by semi-quantitative scoring of immunohistochemically stained frozen tissue sections. Data generated following sampling of tissue from animals with spinal cord lesions, was compared to that obtained using tissue derived from IFA- or saline-injected controls. CRT present in rat serum and in a cohort of human serum derived from 14 multiple sclerosis patients and 11 healthy controls was measured by ELISA.
resultsStained tissue scores revealed significantly (p<0.05) increased amounts of CRT, CHOP and p-eIF2 alpha in the lesion, lesion edge and normal-appearing white matter when compared to controls. CHOP and p-eIF2 alpha were also significantly raised in regions of grey matter and the central canal (p<0.05). Immunofluorescent dual-label staining confirmed expression of these markers in astrocytes, microglia or neurons. Dual staining of rat and human spinal cord lesions with Oil Red O and CRT antibody showed co-localisation of CRT with the rim of myelin fragments. ELISA testing of sera from control and EAE rats demonstrated significant down-regulation (p<0.05) of CRT in the serum of EAE animals, compared to saline and IFA controls. This contrasted with significantly increased amounts of CRT detected in the sera of MS patients (p<0.05), compared to controls.
conclusionThis data highlights the potential importance of CRT and other ER stress proteins in inflammatory demyelination.
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