Oxidative Stress Mechanisms and their Modulation

183 Pages·2014·3.25 MB·English

by  Mohinder Bansal, Naveen Kaushal (auth.)

Mohinder Bansal · Naveen Kaushal
Oxidative Stress
Mechanisms
and their
Modulation
Oxidative Stress Mechanisms
and their Modulation

Mohinder B ansal (cid:129) Naveen Kaushal
Oxidative Stress
Mechanisms and their
Modulation
Mohinder Bansal Naveen Kaushal
Department of Biophysics Department of Biophysics
Panjab University Panjab University
Chandigarh , India Chandigarh , India
ISBN 978-81-322-2031-2 ISBN 978-81-322-2032-9 (eBook)
DOI 10.1007/978-81-322-2032-9
Springer New Delhi Heidelberg New York Dordrecht London
Library of Congress Control Number: 2014948495
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Pref ace
B oth the authors have been involved in oxidative stress-related experimental
research for the past many years, and therefore, an idea was generated to
compile the molecular mechanisms involved in oxidative stress infl uencing
the cell functions and further developing various pathologies.
In this collection, while drafting the contents of the book, two chapters
including the basics of oxidative stress-generating systems and the regulation
of cell signaling by oxidative stress have been included. In the rest of the
chapters, molecular mechanism(s) linking oxidative stress to various patholo-
gies has been taken up. In the end, future perspectives are highlighted on the
subject. Limited fi gures have been included to highlight the important aspects
of the text. At the end of each chapter, references including some reviews
have also been placed for the reader’s convenience for detailed reading on a
particular subject matter.
S ince oxidative stress continues to be a very large fi eld of study with a
great deal of new literature coming up, here the aim was to describe the main
fundamental components in each section to have a generic approach. In this
approach, some research aspects might be overlooked, and therefore, the
authors apologize for that.
The authors feel to convey thanks to all colleagues and associated students
for their direct and indirect contribution during this write-up.
This book is addressed to all scientists interested in starting to work in
oxidative stress research and graduates and postdocs who want to learn
quickly and refer to the molecular mechanisms involved in varying oxida-
tive stress-related pathologies and antioxidant interactions. Also, physi-
cians who want to understand the molecular strategy of the oxidative
stress-related diseases and chemists who want to learn about cellular regu-
lation to fi nd agents to treat related diseases might also have interest in this
book. Overall, this book is a reference aiming at young researchers and
aspiring students to understand the basis and pathophysiological implica-
tion of oxidative stress.
Chandigarh , India Mohinder Bansal
Naveen Kaushal
v

Contents
1 Introduction to Oxidative Stress ................................................... 1
Sources of Oxidative Stress .............................................................. 2
Mitochondria ................................................................................ 2
Cellular Oxidases (NOX and XOR) ............................................. 3
Metal-Catalyzed Reactions .......................................................... 3
Myeloperoxidase (MPO) ............................................................. 3
NO Synthases (NOS) ................................................................... 4
Other Sources ............................................................................... 4
Cellular Redox Status: Free Radicals and Oxidative Stress.
What Are Oxidants? Various Oxygen Radicals ................................ 4
Singlet Oxygen (1O) .................................................................... 5
2
Superoxide Radical (•O− /HO•) .................................................. 5
2 2
Hydrogen Peroxide (HO) .......................................................... 6
2 2
Hydroxyl Radical (OH•) .............................................................. 6
Peroxyl Radicals (ROO•) ............................................................. 6
Reactive Nitrogen Species (RNS) ................................................ 7
Physiological Markers of Oxidative Stress ...................................... 7
8 -Hydroxydeoxyguanosine .......................................................... 8
8 -Nitroguanine ............................................................................. 8
Protein Carbonyls ......................................................................... 9
Inducible Nitric Oxide Synthase .................................................. 9
Nitrotyrosine ................................................................................ 9
Malondialdehydes ........................................................................ 9
F2-Isoprostanes ............................................................................ 9
Oxidative Products of Sugars ....................................................... 10
Redox Ratio (GSH/GSSG) .......................................................... 10
Nuclear Factor-κB ........................................................................ 10
Cyclooxygenase-2 ........................................................................ 10
Glutathione S-Transferase-pi ....................................................... 11
Heme Oxygenase I ....................................................................... 11
Physiological Signifi cance of Oxidative Stress ................................ 11
References ........................................................................................ 14
2 Oxidative Stress in Pathogenesis ................................................... 19
Neurodegenerative Diseases: Parkinson’s
and Alzheimer’s Diseases ................................................................. 19
Role of Pathogenesis in AD and PD ............................................ 20
vii
viii Contents
Electrical and Biological Effects .................................................. 22
Cascades Leading to Dopamine Cell Degeneration ..................... 23
Antioxidants Link in Neurodegenerative Disorders .................... 23
Cardiovascular Diseases ................................................................... 25
Hypercholesterolemia and Atherosclerosis .................................. 25
Hypoxia and Stroke ...................................................................... 27
ROS and Myocardial Infarction ................................................... 28
Antioxidants and CVD ................................................................. 30
Reproductive Systems Disorders (Male and Female) ...................... 30
Male Reproduction ....................................................................... 31
Female Reproduction ................................................................... 35
Role of Antioxidants .................................................................... 39
Autoimmune Diseases ...................................................................... 40
HIV ........................................................................................ 40
Colitis ........................................................................................ 42
Rheumatoid Arthritis .................................................................... 43
References ........................................................................................ 45
Neurodegeneration Diseases ........................................................ 45
Cardiovascular Diseases .............................................................. 47
Male Reproduction ....................................................................... 49
Female Reproductive System ....................................................... 50
Autoimmune Diseases ................................................................. 52
3 Oxidative Stress in Metabolic Disorders/Diseases ....................... 55
Diabetes ............................................................................................ 55
Major Mechanisms of Hyperglycemia- Induced Damage ............ 56
Activation of NF-κB .................................................................... 59
Activation of Stress Kinases (JNK/SAPK and p38 MAPK) ........ 59
Activation of Hexosamine Pathway ............................................. 60
Obesity ............................................................................................. 61
Adipose Tissue/Adipocyte ........................................................... 62
Lipid Oxidation ............................................................................ 62
Oxygen Overconsumption and Increased Metabolic ROS .......... 63
Nutritional and Physiological Antioxidant Defi ciency ................ 63
Chronic Low-Grade Infl ammation ............................................... 64
Aging ................................................................................................ 65
Oxidation of Biomolecules .......................................................... 65
Depletion of Nutrients and Antioxidants ..................................... 67
Cellular Senescence and Death .................................................... 68
Infl ammation ................................................................................ 69
Organelle Dysfunction (Mitochondria) ........................................ 70
Autophagy .................................................................................... 71
References ........................................................................................ 71
Contents ix
4 Oxidative Stress and Carcinogenesis ............................................ 85
Cell-Cycle Regulation by ROS ........................................................ 85
Role of ROS and Oxidative Stress in Initiation, Promotion,
Progression, and Metastasis of Cancers ........................................... 90
Pathways/Networks of p53 Inhibition and Cancer Progression ....... 95
Role of ROS and p53 in Apoptosis ................................................... 97
References ........................................................................................ 98
5 Cell Signaling and Gene Regulation by Oxidative Stress ........... 105
Cell Signaling ................................................................................... 105
Detection of Extracellular Signal by the Receptors ..................... 106
G-Protein-Linked Receptors ........................................................ 106
Ion Channel Linked Receptors ..................................................... 106
Receptor with Intrinsic Enzymatic Activity ................................. 107
Intracellular Receptors ................................................................. 107
Redox Cell Signaling: Cell to Cell Cross Talk ................................. 108
Modulation of Cell Signaling by ROS ............................................. 110
Protein Tyrosine Kinases (PTKs) and Protein
Tyrosine Phosphatases (PTPs) ...................................................... 110
Serine/Threonine Kinases ............................................................. 111
Transcription Factors (TFs) .......................................................... 113
Major Molecular/Metabolic Pathways Affected
by ROS: Infl ammatory Pathways, Stress Response Proteins,
Gene Activation/Repressions, and Antioxidant Strategies ............ 119
References ........................................................................................ 121
6 Managing Oxidative Stress/Targeting ROS ................................. 127
Endogenous: Cellular Antioxidant Defense System ........................ 127
Exogenous: Essential Trace Elements, Vitamins,
Dietary Supplements, and Their Modes of Action ........................... 130
Oxidative Stress-Scavenging Strategies/Targeting:
Endogenous and Exogenous ............................................................. 133
Molecular Network and Modes of Actions
of Antioxidants in Transcriptional Regulation
of ROS and Oxidative Stress ............................................................ 136
Vitamin E ..................................................................................... 136
Carotenoids .................................................................................. 136
Retinoids ...................................................................................... 137
Vitamin C ..................................................................................... 138
Curcumin ...................................................................................... 138
Resveratrol ................................................................................... 139
Flavonoids .................................................................................... 140
Thiol Antioxidants/GSH and Thioredoxin ................................... 141
References ........................................................................................ 142