Reduced Expression of Oligodendrocyte Linage-Enriched Transcripts During the Endoplasmic Reticulum Stress/Integrated Stress Response.

Autor: Gao Y; Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Departments of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA., Slomnicki LP; Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Departments of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA., Kilanczyk E; Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Departments of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA., Forston MD; Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Departments of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA., Pietrzak M; Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio, USA., Rouchka EC; Kentucky Biomedical Research Infrastructure Network Bioinformatics Core, University of Louisville, Louisville, Kentucky, USA., Howard RM; Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Departments of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA., Whittemore SR; Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Departments of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Anatomical Sciences & Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA., Hetman M; Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Departments of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Anatomical Sciences & Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA.; Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Jazyk: angličtina
Zdroj: ASN neuro [ASN Neuro] 2024; Vol. 16 (1), pp. 2371162. Date of Electronic Publication: 2024 Jul 16.
DOI: 10.1080/17590914.2024.2371162
Abstrakt: Endoplasmic reticulum (ER) stress in oligodendrocyte (OL) linage cells contributes to several CNS pathologies including traumatic spinal cord injury (SCI) and multiple sclerosis. Therefore, primary rat OL precursor cell (OPC) transcriptomes were analyzed using RNASeq after treatments with two ER stress-inducing drugs, thapsigargin (TG) or tunicamycin (TM). Gene ontology term (GO) enrichment showed that both drugs upregulated mRNAs associated with the general stress response. The GOs related to ER stress were only enriched for TM-upregulated mRNAs, suggesting greater ER stress selectivity of TM. Both TG and TM downregulated cell cycle/cell proliferation-associated transcripts, indicating the anti-proliferative effects of ER stress. Interestingly, many OL lineage-enriched mRNAs were downregulated, including those for transcription factors that drive OL identity such as Olig2 . Moreover, ER stress-associated decreases of OL-specific gene expression were found in mature OLs from mouse models of white matter pathologies including contusive SCI, toxin-induced demyelination, and Alzheimer's disease-like neurodegeneration. Taken together, the disrupted transcriptomic fingerprint of OL lineage cells may facilitate myelin degeneration and/or dysfunction when pathological ER stress persists in OL lineage cells.
Databáze: MEDLINE