Oxidative Stress: Eustress and Distress

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Oxidative
Stress:
Eustress and Distress
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Contributors
Preface
Part 1: Conceptual
1
Oxidative eustress and oxidative distress: Introductory remarks
	Introduction
		What is new?
	On the development of stress response concepts
	Merits and pitfalls: Usefulness of oxidative stress concept
	Outlook
	Acknowledgments
	References
2
Epistemological challenges of the oxidative stress theory of disease and the problem of biomarkers
	Causation and the OSTD
		Association versus causation: The problem of confounders and reverse causation
			Using Koch’s postulates and Bradford Hill’s criteria in OSTD studies
			Experimental approach to the study of the OSTD
		The problem of multiple causes
	Measuring OS and the problem of biomarkers
		Biomarkers as signs
	Is OS just a biochemical derangement? Physiological support versus pharmacological therapy
	References
	Further reading
3
Systems biology and network medicine: An integrated approach to redox biology and pathobiology
	Introduction
	Introduction to network medicine
		Basic network concepts and network components
		Protein-protein interaction network and the human interactome
			Protein-protein interactions
			Human interactome
			Posttranslational modifications (PTM) of proteins and PPI networks
			Human disease network
	Systems biology approach to understand the redox system
		Redox system
		Mitochondrial molecular networks
		Redox couples and redox environment network
		Protein thiols and redox proteomics
		Network analysis of antioxidant systems
	Omics studies of redox biology and gene regulatory network inference
		Redox transcriptomics and gene regulatory network
		Redox proteomics
		Redox metabolomics
		Integration of multiomic networks
		Dynamic networks and flux analysis
		Network modeling of multicompartment redox system
	Current challenges
	Future directions
	Acknowledgment
	References
4
The reactive species interactome
	Introduction
	Chemical interactions among reactive species
	Characteristics of the reactive species interactome
	Role of the reactive species interactome in the response to stress and evolution of life
	The redox interactome
	The RSI in the context of stratified medicine
	Summary and conclusions
	References
Part 2: Oxidative eustress and distress: Processes and responses
5
Oxidative stress and the early coevolution of life and biospheric oxygen
	Oxygen and the early history of our planet
	Oxygen and life: First contact
	An oxygenic throttle?
	Resistance is not futile
	Rise of the aerobes
	An anaerobic mass extinction?
	Phylogenetic evidence
	Redox biology as an integral part in multicellular evolution
	Conclusion
	Acknowledgments
	References
6
How imaging transforms our understanding of oxidative stress
	Introduction
	Lesson 1: H 2 O 2 is highly compartmentalized
	Lesson 2: Thioredoxin system is powerful regulator of H 2 O 2  patterns
	Lesson 3: Basal H 2 O 2 concentration in the cell is low nanomolar
	Lesson 4: H 2 O 2 transport across membranes is facilitated by aquaporins
	What is missing?
	References
	Further reading
7
In vivo applications of chemogenetics in redox (patho)biology
	Introduction
	Chemogenetics versus optogenetics
	Chemogenetic approaches to study oxidative stress in vivo
	Multiparametric single-cell imaging approaches using chemogenetic tools and genetically encoded biosensors
	References
	Further reading
8
Quantification of intracellular H2O2: Methods and significance
	Introduction
	Biophysical measurement of intracellular H2O2
	Fluorescent reporters
	Kinetic models
	Comparing findings
	Outlook
	References
9
The Keap1-Nrf2 pathway: From mechanism to medical applications
	Introduction
	The discovery of Nrf2
	The discovery of Keap1
	Regulation of Nrf2 by Keap1
	p62-dependent regulation of Nrf2 through a hinge and latch mechanism
	Integration of the Keap1-Nrf2 pathway into the cellular primary metabolism circuitry
	The Keap1-Nrf2 pathway and inflammation
	Future perspectives
	Conclusion
	References
10
Ferroptosis: Physiological and pathophysiological aspects
	A short introduction to the field of cell death
	Ferroptosis: Regulated cell death or just a cellular catastrophe?
	A physiological meaning to ferroptosis?
	Ferroptosis in pathophysiology
	Ferroptosis induction: A promising new anticancer therapeutic strategy
	Concluding remarks
	Acknowledgments
	References
11
Aquaporins: Gatekeepers in the borders of oxidative stress and redox signaling
	Introduction
	An accolade of (mild) stress
	Acute versus chronic stress
	Control of aquaporin-facilitated transmembrane transport upon stress
	Peroxiporins: Surfing between oxidative stress and redox signaling
	References
12
Extracellular superoxide dismutase (SOD3): An antioxidant or prooxidant in the extracellular space?
	Introduction
	Functional regions of SOD3
	Regulation of SOD3 activity
		Transcriptional regulation of SOD3
		Posttranslational regulation of SOD3
		Spatiotemporal regulation of SOD3
	SOD3: An antioxidant in the extracellular space
		SOD3 as a sink for superoxide
		SOD3 in oxidative distress
			Pulmonary disease
			Vascular disease
			Cancer
	SOD3: A prooxidant in the extracellular space
		SOD3 as a source of hydrogen peroxide
		SOD3 in oxidative eustress
			SOD3 in inflammation
				Spatial distribution of SOD3 in inflammation
				Regulation of the inflammatory response
	Conclusion
	Acknowledgments
	References
13
Protein S-glutathionylation and the regulation of cellular functions
	Introduction
	Reversible protein S-glutathionylation
		How do S-glutathionylation reactions regulate proteins in response to physiological cues?
		Nonenzymatic S-glutathionylation reactions do occur in cells
	Protein S-glutathionylation reactions in the cytosol
		Regulation of cytoskeletal dynamics
		Glutaredoxin-1 and neural cell (dys)function
		Apoptosis
		Regulation of kinase signaling cascades
		Role in muscle contraction and relaxation
	Protein S-glutathionylation of mitochondrial proteins
		The mitochondrial matrix favors S-glutathionylation reactions
		Nutrient metabolism and oxidative phosphorylation
			Regulation of the Krebs cycle
			Modulation of complex I
			Regulation of the other respiratory complexes and ATP synthase
		Proton leaks and solute import
		Mitochondrial fission/fusion
	Chemical methods for detecting S-glutathionylated proteins
		Sample treatment
		35 S-labeling and immunoblot
		Switch assays
		Clickable glutathione analogs
		Membrane permeable and intracellular glutathionylation probes
	Conclusions
	References
14
Dual stressor effects of lipid oxidation and antioxidants
	Introduction
	Oxidation of fatty acids and esters
		Enzymatic oxidation of fatty acids and esters
		Nonenzymatic oxidation of fatty acids and esters
	Oxidation of cholesterol
		Enzymatic oxidation of cholesterol
		Nonenzymatic cholesterol oxidation
	Adaptive response to lipid oxidation products: Distress or eustress ?
	Effects of antioxidants
	Summary
	References
15
Oxidized phospholipid signaling: Distress to eustress
	Introduction to redox signaling concepts
	Oxidized phospholipids and their products
	Oxidized lipid signaling versus damage
	Overview of signaling mechanisms for lipid oxidation products: Noncovalent versus covalent interactions
	Examples of the biological effects of oxidized lipids products
		Studies of oxPL mixtures
		Effects of individual oxidized lipids or oxidized lipid families
	Eustress versus distress: A matter of concentration?
	Oxidized lipid signaling: Parallels with hydrogen peroxide-based redox signaling
	Acknowledgments
	References
16
Redox regulation of protein kinase signaling
	Introduction
	Redox-mediated regulation of protein phosphatases
		Protein tyrosine phosphatases (PTPs)
		Serine/threonine phosphatases (PSPs)
	Direct redox regulation of protein kinases
		General concepts
		AGC family
		CAMK family
		CMGC family
		Tyrosine kinase (TK) family
	Redox regulation of phosphoprotein binding
	It is not always cysteine: Importance of other amino acids in redox regulation of kinase signaling
	Achieving specificity in redox-dependent regulation of kinase signaling
		The importance of location
		How does cysteine oxidation affect kinase function?
	Final considerations
	References
17
FoxO transcription factors in the control of redox homeostasis and fuel metabolism
	Introduction
	FoxOs: General aspects
	Molecular mechanisms underlying redox regulation of FoxO transcriptional activity
	Role of FoxOs in the regulation of redox homeostasis and defense against oxidative stress
	Role of FoxOs in the regulation of fuel metabolism
		FoxOs and pancreas
		FoxOs and the liver
		FoxOs and skeletal muscle
		FoxOs and adipose tissue
	Concluding remarks
	References
18
Oxidatively generated DNA base modifications: Relation to eustress and distress
	Introduction
	Oxidative distress at the DNA: Detrimental effects of oxidatively generated DNA damage
		Oxidatively generated DNA damage and cancer risk: General considerations
		DNA damage induced by ROS: Mechanisms and types of lesions
			Reactivity of ROS and DNA damage spectra
			Guanine oxidation products in DNA
			DNA damage spectra by hydroxyl radicals and peroxynitrite
			DNA damage spectra by bromate and tert -butoxyl radicals
			DNA damage spectra by type I photosensitizers and singlet oxygen
		Repair of oxidatively generated DNA base damage
		Endogenously generated DNA damage: Basal levels
		Endogenous sources of oxidatively generated DNA damage
		Relevance of oxidatively generated DNA damage for carcinogenesis
			Lessons from DNA repair defects in human cancers
			Lessons from DNA repair defects in mice
			Lessons from mutation spectra
	Oxidative eustress at the DNA: Physiological effects of oxidatively generated DNA damage
	Conclusions
	References
19
Light-initiated oxidative stress
	Introduction
	Why is light important?
	Some specifics about light
	Light-initiated production of ROS
	Singlet oxygen
		What is ground state oxygen?
		What is singlet oxygen?
			The lowest energy singlet state, O 2 (a 1 Δ g)
			The other singlet state, O 2 (b 1 Σ g +)
		Transitions between states
		How can singlet oxygen be produced by light?
			Energy transfer from a photosensitizer
			Direct irradiation of ground state oxygen
			Dependence on the concentration of ground state oxygen
		What reactions of O 2 (a 1 Δ g) are potentially pertinent to oxidative stress?
		O 2 (a 1 Δ g) as a diffusible signaling agent
		How can the reactions of O 2 (a 1 Δ g) modify/modulate cell redox states and cell response?
			Examples with selected enzymes
			Genetic regulation mediated by O 2 (a 1 Δ g)
		Correlating cell response with the O 2 (a 1 Δ g) reaction in a given cellular location
			Subcellular spatially dependent O 2 (a 1 Δ g)-mediated eustress response
	Superoxide radical anion
		Reactivity of superoxide
		Photoinitiated production of superoxide as a complication
		Selective photoinitiated production of superoxide as a mechanistic tool
	Where does the field stand today? What does the future hold?
		Selective production of O 2 (a 1 Δ g) and superoxide in space and time
		Exploit the opportunity for better control of O 2 (a 1 Δ g) and superoxide dose
		A plethora of new ways to monitor cells and cell response in space and time
	Conclusions
	References
20
Nutritional protection against photooxidative stress in human skin and eye
	Introduction
	Skin
		Skin cancer
		Erythema
		Carotenoids
		Vitamins E and C
		Flavonoids
	Eye
		Cataract
		Age-related macular degeneration (AMD)
	Conclusion
	References
Part 3: Exposome
21
Mechanisms integrating lifelong exposure and health
	Introduction
	Redox theory
		Redox interface
		Redox-responsive elements in complex systems
		Multiomics approaches to understand redox systems
		The redox code
	Exposure memory
	Omics and integrated approaches in oxidative stress research
		Overview of omics technologies and bioinformatics tools for integrative omics
		Biologic response to oxidative stress: Omics studies of low-level cadmium
		Cadmium-epigenome
		Cadmium-transcriptome
		Cadmium-metabolome
		Cadmium-proteome
		xMWAS for integrated omics research
			xMWAS
			Case study: Integrated omics analysis of mouse lung response to cadmium and selenium
	Dynamic responses over time
		Variations in type and impact of exposures
		Multiple omics gives deep phenotyping
		Advantages of systems biology approaches based upon existing knowledgebase
		Cumulative impact on redox networks
		Measures of network flexibility and resilience
	Summary and conclusion
	Funding
	Conflict of interest
	References
22
Nutrient sensing, the oxidative stress response, and stem cell aging
	Introduction
	Nutrient sensing and the oxidative stress response
	Nutrient sensing and the mitochondrial protein folding stress response
	Oxidative stress, stem cell aging, and tissue degeneration
	Therapeutic opportunities
	Conclusion
	Acknowledgments
	References
23
How exercise induces oxidative eustress
	Introduction: Exercise from oxidative stress to eustress
	Worked example 1: NADPH oxidase-mediated O 2 • − production as an exercise-induced redox signal
	Worked example 2: Exercise-induced lipid peroxidation as an exercise-induced redox signal
	When does exercise eustress become oxidative distress?
	Conceptual, technical, and methodological recommendations
	Conclusion
	Acknowledgments
	References
24
Metabolomics as a tool to unravel the oxidative stress-induced toxicity of ambient air pollutants
	Introduction
	Ambient air pollution
	Industrial air toxics
	Traffic-related air pollution
	Occupational exposures
	Ozone
	Discussion
	References
25
Traffic-related environmental risk factors and their impact on oxidative stress and cardiovascular health
	Global burden of pollution, noncommunicable disease, and role of oxidative stress
	The pollutome: Risk factors in the physical environment
		Air pollution: Number one environmental hazard
		Traffic and occupational noise exposures: The underestimated environmental risk factor
	Examples of mechanistic noise studies: Nonauditory effects of noise exposure on oxidative stress and cardiovascular health
		Aircraft noise and translational studies in humans
		Indirect, nonauditory vascular effects of ≤ 100 dB(A) noise exposure
		Indirect, nonauditory pathway activation with aircraft noise exposure  ≤   85 dB(A)
	Other environmental stressors may act in concert with traffic-related exposures by activation of similar oxidative stress a ...
	Conclusions
	Acknowledgments
	Conflicts of interest
	References
	Further reading
Part 4: Oxidative stress in health and disease processes
26
Mitochondrial ROS production during ischemia-reperfusion injury
	Introduction
	Ischemia-reperfusion injury
	Metabolic changes during ischemia
	Mitochondrial superoxide production upon reperfusion following ischemia
	The thermodynamic driving force for RET
	The role of complex I in superoxide production during IR injury
	Induction of the mitochondrial permeability transition pore
	Conclusion
	Funding
	References
	Further reading
27
Redox signaling in cellular differentiation
	Introduction into cellular differentiation
		General targets of ROS in differentiation
		ER stress in differentiation
	ROS in epigenetic mechanisms of cellular differentiation
		DNA methylation
		Histone methylation
		ROS in methylation-controlled differentiation
	Metabolism and ROS in differentiation
		S-adenosylmethionine (SAM) and homocysteine
		Glycolysis in stem cells
	ROS in differentiation of embryonic stem cells
	ROS in differentiation of adult stem cells
		The niche of adult stem cells
		Differentiation of adult stem cells
		Interplay of ROS, Akt, and p38 in adult stem cells
	Transdifferentiation: Epigenetic reprogramming?
	Concluding remarks
	References
28
Redox-regulated brain development
	Oxidative eustress and distress in the brain
	Brain development
	H 2 O 2 signaling during development of the nervous system
		H 2 O 2 production in physiological situations
		Redox regulation of neurogenesis
		Redox regulation of postmitotic neuronal development
	Enzymatic regulation of oxidative eustress in the brain
	Conclusion
	References
29
Eustress, distress, and oxidative stress: Promising pathways for mind-body medicine
	Introduction
	General theories of psychological stress and health
		The origin of stress: A brief history
		Evidence for stressor specificity
		The presence of threat versus the absence of safety
		Distinguishing transdiagnostic distress from diagnosis
		RDoC and neurocircuitry based frameworks
	Eustress: Definition and discordance
		Disentangling exposures and experiences from impact
		Two paths to eustress: Hormesis versus stress buffering
	The assessment of psychological distress
		Standardized tools and tasks
			The validity of self-reported psychological distress
			Self-report measures of perceived stress
			Self-report measures of depressive symptoms
			Self-report measures of anxious symptoms
			Acute laboratory psychological stress tasks
			Neurocognitive tasks
		Naturalistic exposures to stressful life events: Methods and assessment
			Assessing objective stress exposures
			Early adversity
			Daily stressful exposures
			The role of anticipation
	Stress system biomarkers
		Cortisol: Functions and measurement
		Cortisol: No straightforward interpretation
		Cortisol: From eustress to distress
		The autonomic nervous system and oxidative stress
		System allostasis: Robustness and resilience
	Mind-body pathways and oxidative stress markers
		Oxidative damage markers
		Mitochondria
		Nitric oxide and the nitric oxide synthase enzymes
		Antioxidants
	A brief overview of the literature
		Depression, anxiety, and oxidative/nitrosative stress
		PTSD and oxidative/nitrosative stress
		A transdiagnostic perspective
		Translational approaches to eustress
	Oxidative stress as a mediator of psychosocial stress and aging
		Oxidative stress: Explaining the stress-telomere connection
		Cellular senescence: A mechanism of aging
		Deficient autophagy: A promising frontier for eustress research
	A causal role for oxidative stress in depression and anxiety?
		Neuroinflammatory depression & anxiety
		A neuroinflammatory/oxidative subtype of depression/anxiety
		Repeated oxidative stress can trigger and sustain IL-1B
		Evidence of potential clinical relevance
		Inflammation and antidepressant nonresponse
		Oxidative stress as a target for adjunctive treatment
	Eustress, distress, and obesity
		Adipose hypoxia
		Brain-to-adipose pathways
		Adipose-to-brain pathways
		Neuroinflammation in obesity and metabolic disease
		Clinical implications
	Conclusions
	References
30
Reactive oxygen species and cancer
	Introduction
	H2O2 promotes tumorigenesis
	Cancer cells limit damaging lipid hydroperoxide accumulation
	Targeting the redox biology for cancer therapy
	Conclusion
	Acknowledgments
	References
31
Perspectives of TrxR1-based cancer therapies
	Introduction
		TrxR1 in relation to other cellular enzymatic reducing systems
		Cellular and physiological functions of TrxR1
		TrxR1 in health and disease
			Potentially health-promoting effects of high TrxR1 activities
			Potentially health-promoting effects of low TrxR1 activities
			Potentially disease promoting effects of high TrxR1 activities
			Potentially disease promoting effects of low TrxR1 activities
	The intricate roles of TrxR1 in cancer
		Genetic links of TrxR1 to cancer
		Protection against carcinogenesis by TrxR1?
		Promotion of cancer progression by TrxR1
	TrxR1 as a selenoprotein oxidoreductase and the effects of its inhibition
	Drugs targeting TrxR1 for use in cancer therapy
		TrxR1-inhibiting drugs in clinical use for cancer therapy
		Experimental compounds inhibiting TrxR1
	Conclusions and future perspectives
	Acknowledgments
	COI Declaration
	References
32
Oxidative/nitrosative stress and hepatic encephalopathy
	Introduction
	Astrocyte swelling in HE
	Astrocyte swelling and oxidative/nitrosative stress in astrocytes in HE
	Mitochondria and oxidative stress in HE
	Functional consequences of osmotic and oxidative/nitrosative stress in HE
	Oxidative/nitrosative stress and protein tyrosine nitration in HE
	RNA oxidation in HE
	Oxidative/nitrosative stress and gene expression changes in HE
	Oxidative stress and astrocyte senescence in HE
	O-GlcNAcylation and oxidative stress in astrocytes
	Concluding remarks
	Funding
	References
33
ROS signaling in complex systems: The gut
	Introduction
	ROS-generating enzymes in the intestinal mucosa
	ROS in maintenance of intestinal homeostasis
	Intestinal disease: Too much ROS
	Intestinal disease: Not enough ROS
	Conclusions and future directions
	Acknowledgment
	References
34
Oxidative stress in skeletal muscle: Unraveling the potential beneficial and deleterious roles of reactive oxygen species
	Introduction
	Sites of ROS generation in skeletal muscle
	Functions of physiological ROS in muscle
	ROS in muscle degeneration
	Age-related loss of skeletal muscle mass and function
	Oxidative damage and defective redox signaling in muscle from old mice and humans
	Modification of muscle ROS during ageing though knockout of key regulatory proteins
	Role of ROS in denervation and link to ageing
	Denervation of muscle leads to increased muscle mitochondrial generation of peroxides that stimulates muscle atrophy and lo ...
	Implications of the increased mitochondrial peroxide production for prevention of muscle loss with ageing and following den ...
	Future directions in dissection of the roles of redox signaling from oxidative stress in skeletal muscle
	Summary
	Acknowledgments
	References
	Further reading
35
Redox mechanisms in pulmonary disease: Emphasis on pulmonary fibrosis
	Introduction
	ER stress, mitochondrial dysfunction, and the age-associated enhanced susceptibility to lung fibrosis
	Death of lung epithelial cells in fibrosis
	Oxidative stress in lung fibrosis: Glutathione biochemistry
	Protein S-glutathionylation, the death receptor FAS, and epithelial cell death
	ER redox stress and tissue fibrosis
	Concluding comments and challenges for future research and development
	Acknowledgments
		Conflict of Interest
	References
36
Dicarbonyl stress and the glyoxalase system
	Introduction
	Reactive metabolites of dicarbonyl stress: Methylglyoxal, glyoxal, 3-deoxyglucosone, and other α -oxoaldehyde metabolites
	Metabolic drivers of dicarbonyl stress
	Proteins susceptible to modification by methylglyoxal: The dicarbonyl proteome
	Activation of the unfolded protein response by dicarbonyl stress
	Concluding remarks involvement of dicarbonyl stress in aging and disease
	Acknowledgment
	References
	Further reading
37
Redox distress in organ fibrosis: The role of noncoding RNAs
	Introduction
	Fibrosis: Failed resolution of the repair response
	Redox unbalance in fibrosis development
		Oxidative stress in pulmonary fibrosis
		Oxidative stress in kidney fibrosis
		Oxidative stress in liver fibrosis
		Oxidative stress in cardiac fibrosis
		Oxidative stress in skin fibrosis
	Noncoding RNAs in TGF- β /ROS-driven tissue fibrosis
		Regulation of ROS production and antioxidant defense in the fibrotic response
		Regulation of the EMT process in organ fibrosis
		Regulation of TGF- β -induced signaling pathways
		Regulation of other cellular mechanisms involved in organ fibrosis
	Conclusion
	Acknowledgments
	References
Index
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