{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/80468"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/80468","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Elucidating the Role of Store Operated Calcium Entry in Human Oligodendrocyte Progenitor Cells","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Khattab, Heba; 0000-0003-0033-285X"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Sim, Fraser","Pharmacology and Toxicology"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-10-24T19:57:16Z","date_published":"2019-10-24T19:57:16Z","updated_at":"2026-07-27T19:05:23Z","subjects":["pharmacology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/80468","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Sim, Fraser","Pharmacology and Toxicology"]},{"key":"dc:creator","label":"Author","values":["Khattab, Heba; 0000-0003-0033-285X"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-10-24T19:57:16Z","2019","2019-08-27 22:10:01"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["pharmacology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/80468"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","Multiple sclerosis is a chronic inflammatory demyelinating disease characterized by limited neuronal remyelination, which results in impaired saltatory conduction of signals, axonal atrophy and eventually irreversible neurodegeneration. Our previous studies showed that muscarinic receptor (M1/3R) antagonists induced human OPC (hOPC) differentiation and accelerated myelination in an in vivo model of hypomyelination. Furthermore, lentiviral knock down of M3R in hOPCs increased oligodendrocyte differentiation and, in mice, conditional knock out of M3R in OPCs led to enhanced remyelination thus demonstrating an important regulatory role of M3R in OPC differentiation. We found that muscarinic agonist treatment induces intracellular Ca2+ store depletion and subsequent induction of store operated calcium entry (SOCE). SOCE is known to mediate signaling events and regulate gene expression downstream of Gq-coupled receptors such as M3R. In this study, we hypothesized that the SOCE Ca2+ response is necessary for the anti-differentiative effect of M3R and that antagonism of SOCE would block the effect of muscarinic agonist on hOPC differentiation. SOCE is mediated by stromal interaction molecule (STIM1&2), the ER Ca2+ sensor which interacts directly with Orai1, the pore forming element to form a Ca2+ specific channel, CRAC channel. STIM is also reported to activate transient receptor potential canonical 1 (TRPC1) channel which contributes to SOCE currents in many cells."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Elucidating the Role of Store Operated Calcium Entry in Human Oligodendrocyte Progenitor Cells"]}]}],"canonical_facts":{"dc:contributor":["Sim, Fraser","Pharmacology and Toxicology"],"dc:creator":["Khattab, Heba; 0000-0003-0033-285X"],"dc:date":["2019-10-24T19:57:16Z","2019","2019-08-27 22:10:01"],"dc:description":["M.S.","Multiple sclerosis is a chronic inflammatory demyelinating disease characterized by limited neuronal remyelination, which results in impaired saltatory conduction of signals, axonal atrophy and eventually irreversible neurodegeneration. Our previous studies showed that muscarinic receptor (M1/3R) antagonists induced human OPC (hOPC) differentiation and accelerated myelination in an in vivo model of hypomyelination. Furthermore, lentiviral knock down of M3R in hOPCs increased oligodendrocyte differentiation and, in mice, conditional knock out of M3R in OPCs led to enhanced remyelination thus demonstrating an important regulatory role of M3R in OPC differentiation. We found that muscarinic agonist treatment induces intracellular Ca2+ store depletion and subsequent induction of store operated calcium entry (SOCE). SOCE is known to mediate signaling events and regulate gene expression downstream of Gq-coupled receptors such as M3R. In this study, we hypothesized that the SOCE Ca2+ response is necessary for the anti-differentiative effect of M3R and that antagonism of SOCE would block the effect of muscarinic agonist on hOPC differentiation. SOCE is mediated by stromal interaction molecule (STIM1&2), the ER Ca2+ sensor which interacts directly with Orai1, the pore forming element to form a Ca2+ specific channel, CRAC channel. STIM is also reported to activate transient receptor potential canonical 1 (TRPC1) channel which contributes to SOCE currents in many cells."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/80468"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["pharmacology"],"dc:title":["Elucidating the Role of Store Operated Calcium Entry in Human Oligodendrocyte Progenitor Cells"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:23Z"}