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Publié par | justus-liebig-universitat_giessen |
Publié le | 01 janvier 2009 |
Nombre de lectures | 13 |
Langue | English |
Poids de l'ouvrage | 7 Mo |
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FUNCTIONAL CHARACTERIZATION OF
PEROXISOMES AND PATHOLOGICAL
CONSEQUENCES OF PEROXISOMAL
DYSFUNCTION IN THE LUNG
SRIKANTH KARNATI
INAUGURAL DISSERTATION
submitted to the Faculty of Medicine
in partial fulfilment of the requirements
for the PhD-degree of the
Faculties of Veterinary Medicine and Medicine
édition scientifique of the Justus Liebig University Giessen
VVB LAUFERSWEILER VERLAG
VVB LAUFERSWEILER VERLAG ISBN 3-8359-5434-2
STAUFENBERGRING 15
D-35396 GIESSEN
Tel: 0641-5599888 Fax: -5599890
redaktion@doktorverlag.de
www.doktorverlag.de 9 7 8 3 8 3 5 9 5 4 3 4 2
édition scientifique
VVB LAUFERSWEILER VERLAGVVB
KARNATI SRIKANTH PEROXISOMES IN MOUSE AND HUMAN LUNG. Das Werk ist in allen seinen Teilen urheberrechtlich geschützt.
Jede Verwertung ist ohne schriftliche Zustimmung des Autors
oder des Verlages unzulässig. Das gilt insbesondere für
Vervielfältigungen, Übersetzungen, Mikroverfilmungen
und die Einspeicherung in und Verarbeitung durch
elektronische Systeme.
1. Auflage 2009
All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without the prior
written permission of the Author or the Publishers.
st1 Edition 2009
© 2009 by VVB LAUFERSWEILER VERLAG, Giessen
Printed in Germany
édition scientifique
VVB LAUFERSWEILER VERLAG
STAUFENBERGRING 15, D-35396 GIESSEN
Tel: 0641-5599888 Fax: 0641-5599890
email: redaktion@doktorverlag.de
www.doktorverlag.deFunctional characterization of peroxisomes and
pathological consequences of peroxisomal
dysfunction in the lung.
Inaugural Dissertation
submitted to the
Faculty of Medicine
in partial fulfilment of the requirements
for the PhD-degree
of the Faculties of Veterinary Medicine and Medicine
of the Justus Liebig University Giessen
by
Srikanth Karnati
of
Suryapet, India
Giessen 2009
From the Institute for Anatomy and Cell Biology II
of the Faculty of Medicine of the Justus Liebig University of Giessen
Director / Chairperson: Prof. Dr. Eveline Baumgart-Vogt
First Supervisor and Committee Member: Prof. Dr. Eveline Baumgart-Vogt
Second Supervisor and Committee Member: Prof. Dr. Peter Gehr (Bern)
Examination chair and Committee Member: Prof. Dr. Martin Diener
Committee Member: Prof. Dr. Ralph Brehm
Date of Doctoral Defense
th14 Aug 2009
Declaration
“I declare that I have completed this dissertation single-handedly without the
unauthorized help of a second party and only with the assistance acknowledged
therein. I have appropriately acknowledged and referenced all text passages that
are derived literally from or are based on the content of published or unpublished
work of others, and all information that relates to verbal communications. I have
abided by the principles of good scientific conduct laid down in the charter of the
Justus Liebig University of Giessen in carrying out the investigations described in
the dissertation.”
thDate: 14 Aug 2009 (Srikanth Karnati)
Place: Giessen, Germany
My parents
Karnati Swarajya Laxmi, Karnati Sathyanarayana
My wife
Porwal Manvi
And
My family
Table of Contents
1 INTRODUCTION .................................................................................................................. 1
1.1 DISCOVERY OF PEROXISOMES AND PEROXISOMAL ENZYMES .............................................................. 1
1.2 GENERAL FUNCTIONS OF PEROXISOMES ........................................................................................ 2
1.2.1 The peroxisomal β‐oxidation system ................................................... 4
1.2.1.1 Peroxisomal β‐oxidation enzymes ....................................................................... 5
1.2.2 Biosynthetic pathways of cholesterol and ether‐phospholipids in peroxisomes ........ 7
1.3 BIOGENESIS OF PEROXISOMES ..................................................................................................... 7
1.3.1 Peroxisomal targeting signals ............................................................. 8
1.3.2 Docking of the cargo‐receptor complex to the peroxisomal membrane .................... 9
1.3.3 Translocation, dissociation and receptor cycling ...................................................... 10
1.3.4 Import and assembly of peroxisomal membrane proteins ................ 10
1.3.5 Peroxisome growth and division ....................................................... 11
1.3.6 somal diseases ......................................................................... 12
1.4 PATHOLOGICAL CONSEQUENCES OF PEX11β DEFICIENCY ................ 13
1.5 ANIMALS MODELS FOR GENERAL PEROXISOMAL BIOGENESIS DISORDERS (PEX5, PEX2 AND PEX13
KNOCKOUT MICE) ........................................................................................................................ 14
1.6 CONTROL OF PEROXISOME ABUNDANCE AND COMPOSITION BY THE ACTION OF NUCLEAR RECEPTORS ...... 14
1.6.1 Functions of PPARγ in organ systems . 15
1.6.2 PPARs in the lung ....................................................................................................... 16
1.6.3 Molecular mechanisms of PPAR transcription .......................................................... 16
1.7 RESEARCH SO FAR DONE ON PEROXISOMES IN MOUSE AND HUMAN LUNGS .................. 17
1.8 PEROXISOMES IN DEVELOPMENT AND MATURATION OF THE LUNG ........................... 18
1.9 PEROXISOMAL METABOLIC CHANGES DURING TRANSITION OF AECII TO AECI ............. 18
1.10 PEROXISOMES IN HUMAN LUNG DISEASES ................................................................................. 19
2 AIMS OF THE STUDY ......................................................................................................... 20
3 MATERIALS & METHODS .................................................................................................. 22
3.1 EXPERIMENTAL ANIMALS, INSTRUMENTS AND MATERIALS .............................................................. 22
3.1.1 Experimental animals and patient characteristics .................................................... 22
3.2 LABORATORY INSTRUMENTS, GENERAL MATERIALS, PROTEINS AND CHEMICALS ............. 23
3.2.1 Kits ............................................................................... 25
3.2.2 Buffer solutions .......................................................................................................... 26
3.2.3 Antibodies .......................................................................................... 27
3.2.4 Primers ......................................................................... 27
4 METHODS ......................................................................................................................... 30
4.1 TECHNIQUES FOR LIGHT AND FLUORESCENCE MICROSCOPY ............................................................. 30
4.1.1 Fixation of mouse lungs for light microscopy by tracheal instillation . 30
4.