The Three-Body Problem in Stress Biology: The Balance Between O2, NO, and H2S in the Context of Hans Selye’s Stress Concept
Abstract
:1. Introduction
- (1)
- What molecular mechanisms enable a nonspecific response to diverse stressors?
- (2)
- How can the same stressor lead to two opposing outcomes—stress adaptation or stress-induced damage?
2. Stress and Strain in Physics and Engineering: A Foundational Perspective
3. Cannon’s Homeostasis: Introducing the Principle of Balance to Life Sciences
4. Hans Selye’s Original Concept
4.1. Selye’s Concept of Stress
- (1)
- Stress is the nonspecific response of the body to any demand placed upon it.
- (2)
- Stress is inevitable. To be entirely without stress is to be dead!
- (3)
- Stress is not the nonspecific result of damage.
- (4)
- Stress is not something to be avoided.
4.2. Stress as a Biological State: Refinements
- (1)
- The Alarm Stage, characterized by an initial acute response, often exemplified by symptoms like fever during infections.
- (2)
- The Resistance Stage, where adaptation mechanisms stabilize physiological functions.
- (3)
- The Exhaustion Stage, where prolonged or excessive stress exceeds the body’s adaptive capacity, potentially leading to dysfunction or disease.
5. Levitt’s Concepts of Stress and Strain in Plants
5.1. Plant Growth and Environment
5.2. Introduction of Stress and Strain to Plant Science
6. Lichtenthaler’s Application of Chlorophyll Fluorescence as a Marker of Plant Stress
6.1. Four Stages of Plant Stress Responses
6.2. Chlorophyll Fluorescence as a Measure of Stress in Plants
6.3. Broad Applications and Its Limitations
7. Sies’s Concept of Oxidative Stress and Redox Biology
7.1. Oxygen Toxicity
7.2. Oxidative Stress as an Imbalance Between Oxidants and Antioxidants
8. Photooxidative Stress in Plants: The Origin of Oxygen Toxicity
8.1. Oxygenic Photosynthesis as the Origin of Oxygen Toxicity
8.2. Plant Antioxidant Systems and Human Health
8.3. Unification of Plant and Animal Stress Responses by Oxidative Stress
9. The Expanding Universe of Redox Biology
9.1. Updating Oxidative Stress: Integration of Reactive Nitrogen Species (RNS) and Reactive Sulfur Species (RSS)
9.2. Integration of Reactive Nitrogen Species (RNS)
9.2.1. Nitric Oxide (NO) as a Signaling Molecule
9.2.2. Alternative Mechanisms of NO Production
9.3. The Expanding Roles of Reactive Sulfur Species (RSS)
9.3.1. H2S as the Third Gasotransmitter
9.3.2. Endogenous H2S Production in Plants and Animals
9.3.3. Plant-Derived Sulfur Compounds and Human Health
9.4. The Interplay Among ROS, RNS, and RSS
9.4.1. O2-NO-H2S (ONS)
9.4.2. Cysteine Thiol at the Crossroad of Redox Interactions
10. The Three-Body Problem in Stress Biology
10.1. The Dynamic Interplay Among ROS, RNS, and RSS
10.2. Analogy to the Three-Body Problem in Physics
10.3. Broader Implications of the Redox Triad in Stress-Related Diseases
11. Ecological Perspectives: Stress and Neurodegenerative Diseases
11.1. Environmental Stressors and Neurodegeneration
11.2. Natural Neurotoxin BMAA: Linking Disease and Environment
11.3. BMAA and Cyanobacterial Blooms: Global Health Implications
12. The Minimum Machinery for Nonspecific Stress Response
12.1. Multi-Sensitivity of NMDARs
12.2. GLRs in Plants
12.3. TRP Superfamily
12.4. TRP Channels in Response to ONS
12.5. The Minimum Machinery for Selye’s “Filter” Function
13. Updating Selye’s General Adaptation Syndrome (GAS) Model
13.1. O2–NO–H2S (ONS) Homeostasis Model
13.2. Hypoxia: A Distinctive O2–NO–H2S Balance
13.3. Involvement of NO and H2S Productions in Hypoxic Adaptation
14. The Concept of Balance Behind the Opposing Nature of Contributors to the Stress Response: Philosophical Implications
14.1. The Dynamic Harmony of Two Opposites
14.2. The Yin–Yang Principle in Modern Science
14.3. The Balance of Threefold Elements: Evolution of the Yin–Yang Principle
15. Bridging Modern Science and Traditional Medicines While Emphasizing Balance
15.1. Traditional Eastern Medicines
15.2. Acupoints and Meridians
15.3. NO Generation at Acupoints
15.4. Stimulation to a Minimum Machinery
16. Future Perspectives
16.1. O2–NO–H2S (ONS) Dynamics from Physiological, Ecological, and Evolutionary Perspectives
16.2. Special Solutions to the Three-Body Problem in Stress Biology
16.3. The Search for Missing Links
17. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
GAS | General Adaption Syndrome |
ROS | Reactive Oxygen Species |
RNS | Reactive Nitrogen Species |
RSS | Reactive Sulfur Species |
RONSS | Reactive Oxygen, Nitrogen, and Sulfur Species |
iGluR | Ionotropic Glutamate Receptors |
NMDAR | N-methyl-D-aspartate Receptor |
GLR | Glutamate-Receptor-Like Channel |
TRP | Transient Receptor Potential |
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Category | Chemical Formula | Common Name |
---|---|---|
ROS | O2•− | Superoxide |
H2O2 | Hydrogen Peroxide | |
•OH | Hydroxyl Radical | |
1O2 | Singlet Oxygen | |
RNS | NO• | Nitric Oxide |
NO2• | Nitrogen Dioxide | |
ONOO− | Peroxynitrite | |
HNO | Nitroxyl | |
RSS | H2S | Hydrogen Sulfide |
HS− | Hydrosulfide Ion | |
RSSH | Persulfide | |
RSSn− | Polysulfide |
Category | Reactive Species | Modification | Product |
---|---|---|---|
ROS | H2O2 | S-Sulfenylation | Cys–SOH |
HOCl | S-Glutathionylation | Cys–SSG | |
H2O2 (excess) | S-Sulfinylation | Cys–SO2H | |
H2O2 (excess) | S-Sulfonylation | Cys–SO3H | |
RNS | NO• | S-Nitrosylation | Cys–SNO |
ONOO− | S-Nitrosylation | Cys–SNO | |
RSS | H2S | S-Persulfidation | Cys–SSH |
RSSH | S-Persulfidation | Cys–SSH | |
RSS2− | S-Polysulfidation | Cys–SnH | |
CysSSH | Protein S-Polysulfidation | Protein–S–SnH |
Category | Pathology | O2 | NO | H2S | References |
---|---|---|---|---|---|
Cardiovascular Diseases | Myocardial ischemia/infarction | ↓ | ↓ | ↓ | [190,191,192] |
Heart failure | ↓ | ↓ | ↓ | [154,193,194] | |
Pulmonary Disorders | Pulmonary hypertension | ↓ | ↓ | ↓ | [155,195,196] |
COPD/Emphysema | ↓ | ↓ | ↓ | [197,198] | |
Inflammatory Conditions | Rheumatoid arthritis | ↓ | ↑ | ↑ | [199,200,201] |
Inflammatory bowel disease | ↓ | ↑ | ↑ | [202,203,204] | |
Sepsis | ↓ | ↑ | ↑ | [202,205,206] | |
Cancer | Solid tumors | ↓ | ↑ | ↑ | [207,208,209] |
Hematological malignancies | ↓ | ↑ | ↑ | [210,211,212] | |
Metabolic Disorders | Obesity | ↓ | ↓ | ↓ | [213,214,215] |
Diabetes | ↓ | ↓ | ↓ | [214,216,217] | |
Neurodegenerative Disorders | Alzheimer’s disease | ↓ | ↓ | ↓ | [218,219,220] |
Parkinson’s disease | ↓ | ↓ | ↓ | [218,221,222] |
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Yamasaki, H.; Naomasa, R.F.; Mizumoto, K.B.; Cohen, M.F. The Three-Body Problem in Stress Biology: The Balance Between O2, NO, and H2S in the Context of Hans Selye’s Stress Concept. Stresses 2025, 5, 37. https://doi.org/10.3390/stresses5020037
Yamasaki H, Naomasa RF, Mizumoto KB, Cohen MF. The Three-Body Problem in Stress Biology: The Balance Between O2, NO, and H2S in the Context of Hans Selye’s Stress Concept. Stresses. 2025; 5(2):37. https://doi.org/10.3390/stresses5020037
Chicago/Turabian StyleYamasaki, Hideo, Riko F. Naomasa, Kakeru B. Mizumoto, and Michael F. Cohen. 2025. "The Three-Body Problem in Stress Biology: The Balance Between O2, NO, and H2S in the Context of Hans Selye’s Stress Concept" Stresses 5, no. 2: 37. https://doi.org/10.3390/stresses5020037
APA StyleYamasaki, H., Naomasa, R. F., Mizumoto, K. B., & Cohen, M. F. (2025). The Three-Body Problem in Stress Biology: The Balance Between O2, NO, and H2S in the Context of Hans Selye’s Stress Concept. Stresses, 5(2), 37. https://doi.org/10.3390/stresses5020037