Glutamate induced morphological response in astrocytoma cells
department or school: Science, Faculty of
department or school: Science, Irving K. Barber Faculty of (Okanagan)
data provider: DSpace
degree campus: UBCO
creator: Tabatabaee, Mitrasadat
issued: 2021-11-03T19:20:48Z
issued: 2021
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Growing evidence indicates that dysregulation of glutamate signaling between neurons and astrocytes leads to the onset and progression of brain tumors (glioma). The aberrant morphology of glioma cells from astrocytic origin (astrocytoma cells) with elongated processes is also emerging as an underlying cause of progression and therapy resistance of gliomas. Whether glutamate dysregulation conducts this atypical morphology of astrocytoma cells has not been explored. Since normal astrocytes respond to glutamate by filopodiagenesis and processes extension, observing aberrantly elongated processes in response to excessive glutamate in astrocytoma cells is conceivable; yet it requires detailed empirical support to make it translatable to therapies. In this dissertation, the role of glutamate receptors and contribution of L-type voltage-gated calcium channels (CaVs) in elongation and directional protrusion of the astrocytoma cell processes toward glutamate were investigated. Protrusion of cellular processes toward glutamate and an intracellular calcium rise were observed in U118-MG astrocytoma cells. α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), whose role in neuro-gliomal interactions has been reported, did not trigger filopodiagenesis in these cells. In contrast, use of selective agonists (kainate and phenyl-kainate) and an antagonist (CNQX) indicated that kainate receptors (KARs) contribute to the glutamate-induced morphological response. However, precisely releasing a KAR caged-agonist (DECM-PhKA) to the 3D-cultured cells showed that despite their role in processes extension, KARs do not contribute to the pathfinding and the directional motility towards glutamate. CaVs were also found to play a role in the glutamate-induced morphological response in U118-MG cells by using selective antagonists (nifedipine, verapamil and diltiazem). Interestingly, a real-time imaging probe (FluoBar1) revealed that the membranar density of CaV1.2 rises immediately upon exp…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/80143
note: i GLUTAMATE INDUCED MORPHOLOGICAL RESPONSE IN ASTROCYTOMA CELLS by Mitrasadat Tabatabaee Ph.D. ISLAMIC AZAD UNIVERSITY (Tehran Science and Research) Tehran, Iran, 2010 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE COLLEGE OF GRADUATE STUDIES (Biochemistry and Molecular Biology) THE UNIVERSITY OF BRITISH COLUMBIA (Okanagan) October 2021 © Mitrasadat Tabatabaee, 2021 ii The following individuals certify that they have read, and recommend to the College of Graduate Studies for acceptance, a thesis/dissertation entitled: Studying the morphological response induced by glutamate in astrocytoma cells submitted by Mitrasadat Tabatabaee in partial fulfillment of the requirements of the degree of Doctor of philosophy. Dr. Frederic Menard; I.K. Barber Faculty of science, University of British Columbia (Okanagan) Supervisor Dr. Mark Rheault; I.K. Barber Faculty of science, University of British Columbia (Okanagan) Supervisory Committee Member Dr. Andis Klegeris; I.K. Barber Faculty of science, University of British Columbia (Okanagan) Supervisory Committee Member Dr. Michael A Russello; I.K. Barber Faculty of science, University of British Columbia (Okanagan) University Examiner Dr. Keith Murai; Faculty of medical and health sciences, University of McGill External Examiner iii Abstract Growing evidence indicates that dysregulation of glutamate signaling between neurons and astrocytes leads to the onset and progression of brain tumors (glioma). The aberrant morphology of glioma cells from astrocytic origin (astrocytoma cells) with elongated processes is also emerging as an underlying cause of progression and therapy resistance of gliomas. Whether glutamate dysregulation conducts this atypical morphology of astrocytoma cells has not been explored. Since normal astrocytes respond to glutamate by filopodiagenesis and processes extension, observing aberrantly elongated processes in response to excessive glutamate in astro…
has type: Thesis/Dissertation
date issued: 2021-11
is shown at: 10.14288/1.0402936
language: eng
degree discipline: Biochemistry and Molecular Biology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Menard, Frederic
type: Text
identifier URI: http://hdl.handle.net/2429/80143