Cell Growth and Cholesterol Esters

149 Pages·2005·3.767 MB·English

by  Alessandra Pani, Sandra Dessi

MOLECULAR BIOLOGY INTELLIGENCE UNIT
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ISBN 0-306-48236-3
9780306 482366
M B
OLECULAR IOLOGY
I
NTELLIGENCE
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NIT
Cell Growth
and Cholesterol Esters
Alessandra Pani, Ph.D.
Department of Biomedical Sciences and Technologies
Section of General Microbiology and Virology
and Microbial Biotechnologies
University of Cagliari
Cittadella Universitaria
Monserrato, Italy
Sandra Dessì, Ph.D.
Department of Biomedical Science and Biotechnologies
Section of Experimental Pathology
University of Cagliari
Cagliari, Italy
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C G C E
ELL ROWTH AND HOLESTEROL STERS
Molecular Biology Intelligence Unit
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Cell Growth and Cholesterol Esters, edited by Alessandra Pani and Sandra Dessi, Landes / Kluwer dual imprint /
Landes series: Molecular Biology Intelligence Unit
ISBN: 0-306-48236-3
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Library of Congress Cataloging-in-Publication Data
Cell growth and cholesterol esters / [edited by] Alessandra Pani, Sandra
Dessì.
p. ; cm. -- (Molecular biology intelligence unit)
Includes bibliographical references and index.
ISBN 1-58706-193-7
1. Cholesterol--Metabolism. 2. Esterification. 3.
Cells--Growth--Regulation.
[DNLM: 1. Cholesterol Esters--metabolism. 2. Cell Division--drug
effects. 3. Esterification. QU 95 C393 2003] I. Pani, Alessandra. II.
Dessì, Sandra. III. Molecular biology intelligence unit (Unnumbered)
QP752.C5C44 2003
571.8'4--dc22
2003014862
Dedication
To Giovanni, Mario and Laura
CONTENTS
Preview .................................................................................................xi
1. Overview—Intracellular Cholesterol Homeostasis:
Old and New Players .............................................................................1
Sandra Dessì and Barbara Batetta
Acquisition of Cholesterol by Peripheral Cells.......................................1
Endogenous Synthesis...........................................................................1
Exogenous Uptake: The LDL Receptor Pathway...................................2
Mechanisms of Cholesterol Homeostasis...............................................4
Involvement of MDR1-P-gp in Cholesterol Transport..........................4
Sterol Regulatory Systems in the ER......................................................6
Metabolic Fate of Cytoplasmic Lipid Droplets......................................8
Efflux of Cholesterol .............................................................................8
HDL Metabolism..................................................................................8
HDL Receptors.....................................................................................9
Conclusions.........................................................................................10
2. Role of Mevalonate Derivatives in Cell Cycle Progression....................13
Sandra Dessì
Cholesterol and Cell Growth...............................................................13
Role of Mevalonate in DNA Synthesis ................................................16
Loss of Feedback Control of Cholesterol Synthesis
in Malignant States..........................................................................16
Mevalonate and Protein Prenylation....................................................17
Protein Prenylation .............................................................................17
Family of GTP-Binding Proteins (G Proteins) ....................................18
Ras Superfamily...................................................................................18
The Role of Farnesylation in Ras Function..........................................18
Ras Encoded G Protein Signaling Cascade..........................................18
Role of Cholesterol in the Formation of Rafts
and Signal Transduction..................................................................20
Conclusions.........................................................................................21
3. Cholesterol Esters and Cell Growth: Coregulation in Animal Models...25
Sandra Dessì and Barbara Batetta
Cholesterol Esters Regulation in Vivo .................................................25
Cholesterol Esters and Cell Growth in Experimental Animals.............27
Cholesterol Ester Metabolism in Experimental Models
Involving Normal Liver Growth Activation.....................................28
Cholesterol Ester Metabolism in Experimental Models
Involving Extrahepatic Growth Activation ......................................29
The Inhibition of Cholesterol Esterification Suppress
the Proliferative Capacity of an Organ.............................................30
Cholesterol Esterification during Tumor Growth................................30
Alterations of Cholesterol Esterification in Proliferating
Tissues Are Associated with Peculiar Changes of Lipid
Metabolism in the Plasma Compartment........................................31
Conclusions.........................................................................................33
4. Cholesterol Metabolism in Human Tumors.........................................35
Sandra Dessì and Barbara Batetta
Lipoprotein Metabolism and Human Cancer......................................35
General Pathway of Lipoprotein Metabolism: An Overview................35
Hypocholesterolemia and Human Tumors..........................................39
Lipoprotein Metabolism in Hematologic Neoplasms...........................40
Lipoprotein Metabolism in Solid Tumors...........................................42
Serum Lipid Profiles in Non-Tumoral Human Proliferative Disease...45
Cholesterol Metabolism in Tumoral Tissues .......................................46
Conclusions.........................................................................................47
5. The Mobilization of Cholesterol Released at Sites of Tissue Injury......50
Robert Kisilevsky and Shui-Pang Tam
Serum Amyloid A (SAA).....................................................................51
What Is the Physiologic Function of Acute Phase SAA?.......................52
The Influence of SAA on Macrophage Cholesterol
Metabolism during Inflammation ...................................................55
SAA, Atherogenesis, Unstable Angina, and Prognosis
of Myocardial Infarction..................................................................60
6. Cholesterol Esters and Cell Growth in Human Lymphocytes:
Possible Implication of P-gp Modulators.............................................65
Francesca Sanna, Marirosa Putzolu and Barbara Batetta
Introduction........................................................................................65
Proposed Roles of P-gp in Cell Physiology ..........................................66
Time-Dependent Changes in Cholesterol Ester Synthesis
and MDR1 and ACAT Gene Expressions in Lymphocytes
Stimulated to Growth by PHA........................................................67
P-gp Inhbition Suppresses Proliferation of PHA Stimulated
Lymphocytes...................................................................................67
In PHA Stimulated Lymphocytes, MDR1 Gene Expression
Is Not Correlated to a MDR Phenotype..........................................68
Progesterone Treatment Increased Raft-Cholesterol Content
in PHA-Stimulated Lymphocytes....................................................69
Conclusions.........................................................................................69
7. Cholesterol Esterification and MDR1-P-gp in Lymphoblastic
Leukemia Cells: Functional Relationships............................................72
Rosa Rita Bonatesta and Barbara Batetta
Introduction........................................................................................72
Altered Cholesterol Balance during Tumoral Growth..........................72
Positive Correlation between Growth Rate and Cholesterol
Esterification in CEM and MOLT4 Cell Lines...............................73
A Role for P-gp in the Lipid Transport of Leukemia Cells...................76
Conclusions.........................................................................................77
8. MDR-1, Cell Growth and Cholesterol Esterification ...........................81
Alessandra Pani and Sandra Dessì
Multidrug Resistance...........................................................................81
P-gp and MDR...................................................................................81
P-gp Substrates and Antagonists..........................................................83
P-gp Tissue Localization and Physiologic Function(s) .........................84
P-gp in Cell Death and Cell Growth...................................................86
P-gp Involvement in Intracellular Cholesterol Trafficking...................86
P-gp, Cell Growth and Cholesterol Esterification................................89
Conclusions.........................................................................................92
9. Involvement of Cholesterol Ester Cycle in the Progression
of Atherosclerosis .................................................................................98
Maria Franca Mulas and Sandra Dessì
Structure of the Normal Arteries .........................................................98
Lesions of Atherosclerosis....................................................................99
Pathogenesis of Atherosclerosis..........................................................100
Plaque Rupture .................................................................................101
Roles of Cell Proliferation and Cholesterol Ester Accumulation
in the Pathogenesis of Atherosclerosis............................................101
Proliferating Cells in the Artery Wall.................................................102
Cholesterol Ester Accumulation ........................................................104
Cholesterol Ester Cycle .....................................................................104
Cholesterol Efflux..............................................................................105
Possibility of a Link between Cholesterol Esterification
and Cell Proliferation during Atherogenesis...................................106
Conclusions.......................................................................................107
10. Role of Cholesterol Esterification in the Modulation
of Vascular Smooth Muscle Cell (VSMC) Cycle.................................111
Maria Franca Mulas and Sandra Dessì
Human Vascular Proliferative Diseases..............................................111
VSMC Proliferation..........................................................................112
Cell Cycle Regulation of Vascular Muscle Cell Proliferation .............113
Molecular Regulation of Proliferation and Potential
Therapeutic Applications...............................................................114
VSMC Cycle and Cholesterol Esterification Pathway........................114
Possible Mechanisms by Which Cholesterol Esterification
May Regulate VSMC Proliferation................................................116
Hypothetical Model by Which Cholesterol Esterification
Induces VSMC..............................................................................117
Conclusions.......................................................................................119
11. MDR, Cell Growth and Cholesterol Esterification:
Implications for Cancer Therapy........................................................122
Alessandra Pani and Sandra Dessì
Anti-Cancer Chemotherapy ..............................................................123
Variables of the Cancer Response to Chemotherapy..........................124
MDR and Cancer..............................................................................125
MDR Modulators in Clinical Trials..................................................126
Clinical Significance of P-gp Expression in Cancer............................127
Other Mechanisms by Which P-gp Inhibitors May Block
Cancer Progression........................................................................128
Conclusions.......................................................................................129
Index..................................................................................................135
EDITORS
Alessandra Pani, Ph.D.
Department of Biomedical Sciences and Technologies
Section of General Microbiology and Virology
and Microbial Biotechnologies
University of Cagliari
Cittadella Universitaria
Monserrato, Italy
Chapters 8, 11
Sandra Dessì, Ph.D.
Department of Biomedical Science and Biotechnologies
Section of Experimental Pathology
University of Cagliari
Cagliari, Italy
Chapter 1, 2, 3, 4, 8, 9, 10, 11
CONTRIBUTORS
Barbara Batetta Robert Kisilevsky
Department of Biomedical Science Departments of Pathology
and Biotechnologies and Biochemistry
Section of Experimental Pathology Queen’s University and
University of Cagliari The Syl and Molly Apps Research Center
Cagliari, Italy Kingston General Hospital
Chapters 1, 3, 4, 6, 7 Kingston, Ontario, Canada
Chapter 5
Rosa Rita Bonatesta
Department of Biomedical Science Maria Franca Mulas
and Biotechnologies Department of Biomedical Science
Section of Experimental Pathology and Biotechnologies
University of Cagliari Section of Experimental Pathology
Cagliari, Italy University of Cagliari
Chapter 7 Cagliari, Italy
Chapters 9, 10
Marirosa Putzolu
Department of Biomedical Science
and Biotechnologies
Section of Experimental Pathology
University of Cagliari
Cagliari, Italy
Chapter 6
Francesca Sanna Shui-Pang Tam
Department of Biomedical Science Department of Biochemistry
and Biotechnologies Queen’s University and
Section of Experimental Pathology The Syl and Molly Apps Research Center
University of Cagliari Kingston General Hospital
Cagliari, Italy Kingston, Ontario, Canada
Chapter 6 Chapter 5