96300da98b79952be9ac2e4038f1f6ee ijmolsci_a2022v23n7p3617.pdf 75b30d3e92a6adc52f0500e1920be02488118b74 ijmolsci_a2022v23n7p3617.pdf 7c9b80d08aa13832c42c477aebd94ebb8452fe91be78352dd4d87c8a873399c9 ijmolsci_a2022v23n7p3617.pdf Title: TRPV2: A Key Player in Myelination Disorders of the Central Nervous System Subject: Transient potential receptor vanilloid 2 (TRPV2) is widely expressed through the nervous system and specifically found in neuronal subpopulations and some glial cells. TRPV2 is known to be sensitized by methionine oxidation, which results from inflammation. Here we aim to characterize the expression and regulation of TRPV2 in myelination pathologies, such as hypomyelination and demyelination. We validated the interaction between TRPV2 and its putative interactor Opalin, an oligodendrocyte marker, in mixed glial cultures under pro- and anti-inflammatory conditions. Then, we characterized TRPV2 time-course expression in experimental animal models of hypomyelination (jimpy mice) and de-/remyelination (cuprizone intoxication and experimental autoimmune encephalomyelitis (EAE)). TRPV2 showed upregulation associated with remyelination, inflammation in cuprizone and EAE models, and downregulation in hypomyelinated jimpy mice. TRPV2 expression was altered in human samples of multiple sclerosis (MS) patients. Additionally, we analyzed the expression of methionine sulfoxide reductase A (MSRA), an enzyme that reduces oxidated methionines in TRPV2, which we found increased in inflammatory conditions. These results suggest that TRPV2 may be a key player in myelination in accordance with the recapitulation hypothesis, and that it may become an interesting clinical target in the treatment of demyelination disorders. Keywords: transient potential receptor vanilloid 2; Opalin; oxidative stress; myelination; multiple sclerosis; recapitulation theory Author: Jennifer Enrich-Bengoa, Gemma Manich, Tony Valente, Paula Sanchez-Molina, Beatriz Almolda, Carme Solà, Josep Saura, Berta González, Bernardo Castellano and Alex Perálvarez-Marín Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Mar 28 10:27:01 2022 CEST ModDate: Tue Mar 29 04:23:50 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 24 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4387761 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OTZEDH+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 ARIQJE+VnURWPalladioL Type 1 Custom yes yes no 15 0 EEMZWB+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 DJHNHH+URWPalladioL-Roma Type 1 Custom yes yes 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WinAnsi yes yes no 312 0 GGLIDA+Calibri,Bold CID TrueType Identity-H yes yes yes 315 0 GGLKDF+Arial,Bold CID TrueType Identity-H yes yes yes 321 0 GIZSCG+EURM7 Type 1 Builtin yes yes no 343 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 362 0 GGJNPL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 376 0 GGJNPN+PalatinoLinotype TrueType WinAnsi yes yes no 379 0 GGJOAP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 382 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-02 02:28:02 CEST RepresentationInformation: ijmolsci_a2022v23n7p3617.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-03-29 12:34:18 CEST Size: 4387761 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 711 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Opalin Interacts In Vitro with the Ankyrin-Repeat Domain (ARD) of TRPV2 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: TRPV2 and Opalin Display a High Degree of Colocalization in Mixed Glial Cultures Enriched in Oligodendrocytes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: TRPV2 Expression in Microglia and Oligodendrocytes Is Regulated after Pro-Inflammatory, Anti-Inflammatory and Demyelinating Treatments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: TRPV2 and Opalin Expression, but Not Methionine Sulfoxide Reductase A (MSRA) Levels, Are Importantly Reduced in the Hypomyelinating Jimpy Mutant Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: TRPV2 and MSRA Expression Are Modulated in the Experimental Mouse Models of MS: The Cuprizone and the EAE Models Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: MSRA and TRPV2 Gene and Protein Expression Are Modified in Frontal Cortex Samples of MS Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Children: Item: Title: Animals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Cuprizone-Induced Demyelination and Remyelination in Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Experimental Autoimmune Encephalomyelitis in Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Human Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: FL and ARD TRPV2 Fragment Purification Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Slot Blot Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Cell Cultures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Cell Culture Treatments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Nitrite Assay Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Immunocytochemistry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Colocalization Studies of Opalin and TRPV2 in Cell Cultures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Quantification of TRPV2 in Glial Cell Cultures by Enzyme-Linked Immunosorbent Assay Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Tissue Fixation and Processing for Immunohistochemistry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Immunohistochemistry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Quantification of Immunohistochemical Stainings Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: Double Immunohistochemistry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: Isolation of Total Proteins Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Quantification of TRPV2 and MSRA in EAE Mouse and Human Samples by Western Blot Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: RNA Extraction, cDNA Synthesis and Expression Analyses in Human Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Info: Title: TRPV2: A Key Player in Myelination Disorders of the Central Nervous System Author: Jennifer Enrich-Bengoa, Gemma Manich, Tony Valente, Paula Sanchez-Molina, Beatriz Almolda, Carme Solà, Josep Saura, Berta González, Bernardo Castellano and Alex Perálvarez-Marín Subject: Transient potential receptor vanilloid 2 (TRPV2) is widely expressed through the nervous system and specifically found in neuronal subpopulations and some glial cells. TRPV2 is known to be sensitized by methionine oxidation, which results from inflammation. Here we aim to characterize the expression and regulation of TRPV2 in myelination pathologies, such as hypomyelination and demyelination. We validated the interaction between TRPV2 and its putative interactor Opalin, an oligodendrocyte marker, in mixed glial cultures under pro- and anti-inflammatory conditions. Then, we characterized TRPV2 time-course expression in experimental animal models of hypomyelination (jimpy mice) and de-/remyelination (cuprizone intoxication and experimental autoimmune encephalomyelitis (EAE)). TRPV2 showed upregulation associated with remyelination, inflammation in cuprizone and EAE models, and downregulation in hypomyelinated jimpy mice. TRPV2 expression was altered in human samples of multiple sclerosis (MS) patients. Additionally, we analyzed the expression of methionine sulfoxide reductase A (MSRA), an enzyme that reduces oxidated methionines in TRPV2, which we found increased in inflammatory conditions. These results suggest that TRPV2 may be a key player in myelination in accordance with the recapitulation hypothesis, and that it may become an interesting clinical target in the treatment of demyelination disorders. 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