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Doraids Final Master Thesis Exploring G-Protein-Coupled Receptors Regulation, Specificity and Controllability of Exosomes Release in the Neuronal Cell Line SH-SY5Y Item Type text; Electronic Thesis Authors Sadideen, Doraid Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 08/10/2021 20:16:18 Link to Item http://hdl.handle.net/10150/621166 EXPLORING G-PROTEIN-COUPLED RECEPTORS REGULATION, SPECIFICITY AND CONTROLLABILITY OF EXOSOMES RELEASE IN THE NEURONAL CELL LINE SH-SY5Y By Doraid Tarek Sadideen ____________________________ A Thesis Submitted to the Faculty of the GRADUATE INTERDISCIPLINARY PROGRAM IN PHYSIOLOGICAL SCIENCES In Partial Fulfillment of the Requirements For the Degree of MASTER OF SCIENCE In the Graduate College THE UNIVERSITY OF ARIZONA 2016 1 STATEMENT BY AUTHOR This thesis has been submitted in partial fulfillment of requirements for an advanced degree at the University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library. Brief quotations from this thesis are allowable without special permission, provided that an accurate acknowledgement of the source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his or her judgment the proposed use of the material is in the interests of scholarship. In all other instances, however, permission must be obtained from the author. SIGNED: Doraid Tarek Sadideen APPROVAL BY THESIS DIRECTOR This thesis has been approved on the date shown below: Torsten Falk Date Assistant Professor of Neurology August 5th 2016 2 ACKNOWLEDGMENT This thesis was possible with the support of: Torsten Falk, Brian S. McKay, Scott J. Sherman, my parents (Tarek Sadideen and Suhair Amer), and siblings (Zeyad, Rana, Yousra and Ayah Sadideen). As well as a handful of people at the University of Arizona’s Physiological Sciences Graduate Interdisciplinary Program (PSGIDP). 3 TABLE OF CONTENTS Chapter Page No. List of Figures ......................................................................................................................... 6 List of Tables .......................................................................................................................... 8 List of Abbreviations ............................................................................................................... 9 Abstract ................................................................................................................................ 10 Introduction .......................................................................................................................... 11 General introduction ...................................................................................................................... 11 Parkinson’s disease ........................................................................................................................ 11 Alpha-Synuclein ............................................................................................................................. 16 Exosomes ....................................................................................................................................... 18 SH-SY5Y .......................................................................................................................................... 19 CHO-K1 .......................................................................................................................................... 20 MCF-7 ............................................................................................................................................ 21 Aims of project ............................................................................................................................... 22 Materials and Methods ......................................................................................................... 24 Materials ........................................................................................................................................ 24 Cell lines ............................................................................................................................................. 24 Antibodies .......................................................................................................................................... 24 General lab reagents ......................................................................................................................... 24 Plasmid .............................................................................................................................................. 25 Viral α-SYN and GFP ........................................................................................................................... 25 Methods ........................................................................................................................................ 25 Cell culture ......................................................................................................................................... 25 Plasmid preparation .......................................................................................................................... 26 Agarose gel electrophoresis of DNA .................................................................................................. 28 Transient transfection of DNA ........................................................................................................... 28 Medium collection and cell harvest ................................................................................................... 29 Bradford protein assay ...................................................................................................................... 30 Exosome-depleted serum .................................................................................................................. 30 Cell differentiation ............................................................................................................................. 30 Exosome isolation .............................................................................................................................. 31 SDS-Polyacrylamide gel electrophoresis ............................................................................................ 31 Western blotting ................................................................................................................................ 32 Silver stain ......................................................................................................................................... 33 Exosome labeling ............................................................................................................................... 33 Exosomes specificity and uptake ....................................................................................................... 34 4 Biotinylation of exosomes ................................................................................................................. 36 Viral α-SYN and GFP transduction ..................................................................................................... 38 Results .................................................................................................................................. 39 Transient transfection of DNA ........................................................................................................... 39 Cell differentiation ............................................................................................................................. 41 Silver stain ......................................................................................................................................... 43 Exosomes specificity and uptake ....................................................................................................... 44 Biotinylation of exosomes ................................................................................................................. 47 Discussion ............................................................................................................................. 48 References ............................................................................................................................ 52 5 List of Figures Figure 1: Cross section of post-mortem midbrain from a human patient with PD (P) and a control (C) (37), reprinted with permission from BCMJ2001. ......................................................... 13 Figure 2: Lewy bodies (arrows) in the SNpc, visualized through a hematoxylin-eosin stain (32), reprinted with permission from John Wiley and Sons 2014. ................................................ 13 Figure 3: Schematic representation of α-SYN. (A) The regions of α-SYN and most common point-mutations (28, 29), reprinted with permission from Cambridge University Press 2014. (B) Representation of α-SYN in its micelle-bound form (28, 30), reprinted with permission from Nature Publishing Group 2012.
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