GO:0034465 response to carbon monoxide: Cellular Stress Response, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0034465 response to carbon monoxide describes any process that changes a cell or organism's state or activity in response to a carbon monoxide (CO) stimulus, including movement, secretion, enzyme production, and gene expression.
• CO is not only a toxic gas; at low doses it acts as a signaling molecule that modulates ventilation, erythropoiesis, inflammation, and neuronal activity.
• The ventilatory response to CO is driven primarily by carotid body chemoreceptors and involves changes in breathing pattern and blood pressure regulation.
• Low-level CO exposure alters blood oxygenation level-dependent (BOLD) fMRI signals, indicating that CO-responsive pathways influence neurovascular coupling.
• CO levels correlate with symptom severity and autoimmunity in children with autism spectrum disorder, and respond to probiotic treatment, linking this GO term to host-microbe interactions.
• Studying GO:0034465 requires integrated models including knockout, knock-in, and overexpression cell lines, animal exposure systems, and multi-omics readouts.
Description
GO:0034465 response to carbon monoxide is a biological process ontology term that captures the full range of cellular and organismal changes triggered by carbon monoxide (CO). CO is a colorless, odorless gas historically known for its toxicity, but research over the past two decades has revealed that it also functions as a gasotransmitter with physiological signaling roles at low concentrations. The term encompasses diverse responses such as altered ventilation, changes in gene expression, modified enzyme activity, and shifts in blood flow and neuronal activity. Understanding this process is critical for toxicology, neuroscience, and therapeutic development because CO exposure can be accidental, environmental, or intentional as a potential therapeutic agent. Researchers studying GO:0034465 aim to map the molecular sensors, signaling cascades, and physiological outputs that define how organisms detect and react to CO. This article integrates authoritative QuickGO annotation data with verified PubMed literature to provide a research-grade overview of the genes, mechanisms, and experimental models relevant to this term.
response to carbon monoxide At A Glance
| GO ID | GO:0034465 |
|---|---|
| GO term | response to carbon monoxide |
| Ontology | biological_process |
| Synonym | None listed in QuickGO |
| Major function | Mediates cellular and organismal changes in response to carbon monoxide stimulus, including ventilatory, vascular, inflammatory, and gene expression responses |
| Definition source | QuickGO definition: Any process that results in a change in state or activity of a cell or an organism as a result of a carbon monoxide (CO) stimulus |
| Related stimuli | Carbon monoxide gas, CO-releasing molecules (CORMs), endogenous CO from heme oxygenase activity |
| Key physiological outputs | Ventilation changes, erythropoietin induction, BOLD fMRI signal alteration, inflammatory modulation |
| Taxonomic range | Annotation across metazoans including mammals such as Homo sapiens, Mus musculus, and Sus scrofa |
What Is GO:0034465?
According to the Gene Ontology, GO:0034465 response to carbon monoxide is defined as any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a carbon monoxide (CO) stimulus. This definition is intentionally broad, covering rapid physiological reflexes such as ventilatory changes as well as slower adaptive responses including altered gene transcription and protein function. The term is classified under biological_process and has no synonyms in the current QuickGO release. It is used to annotate gene products that are causally involved in detecting CO, transducing the CO signal, or executing downstream cellular responses.
Why Is response to carbon monoxide Important in Cell Biology?
GO:0034465 is important because carbon monoxide is a ubiquitous environmental toxicant and an endogenous signaling molecule, and the biological response to CO determines outcomes ranging from acute poisoning to therapeutic benefit. Understanding this process helps researchers develop antidotes, optimize CO-based therapies, and interpret physiological data such as fMRI signals that are influenced by CO levels. Moreover, CO-responsive pathways intersect with oxygen sensing, inflammation, and erythropoiesis, making this term relevant to diverse fields including neuroscience, hematology, and immunology.
• CO exposure is a leading cause of accidental poisoning worldwide, and the response to CO determines survival and long-term outcomes.
• Low-dose CO has shown anti-inflammatory and cytoprotective effects in preclinical models of sepsis and organ injury.
• The ventilatory response to CO is a classic reflex studied to understand chemoreception and respiratory control.
• CO alters BOLD fMRI signals, which has implications for interpreting functional brain imaging in humans and animals.
• CO levels correlate with symptom severity and autoimmunity in autism spectrum disorder, suggesting a role in neuroimmune interactions.
• Erythropoietin induction by CO exposure differs between males and females, highlighting sex-specific responses.
• Retinal venous CO responds to bright light, linking this GO term to visual physiology and phototransduction.
• CO-releasing molecules are being developed as therapeutics, requiring precise understanding of the response to CO.
• Probiotic treatment alters CO levels in children with ASD, indicating that the microbiome can modulate this response.
• Studying GO:0034465 supports the development of biomarkers and interventions for CO-related pathologies.
What Happens During response to carbon monoxide?
CO Sensing and Chemoreception
In simple terms: The body detects carbon monoxide primarily through sensors in the carotid body, which triggers a reflex to increase breathing.
The initial step in the response to carbon monoxide involves detection by peripheral chemoreceptors, particularly the carotid body. Santiago et al. demonstrated that the ventilatory response to CO is mediated by the carotid body and involves changes in breathing pattern and blood pressure. This sensing mechanism is critical for rapid physiological adjustments to CO exposure. The exact molecular sensors for CO are still being elucidated, but heme-containing proteins are likely candidates given CO's high affinity for heme iron.
Ventilatory and Cardiovascular Adjustments
In simple terms: Once CO is sensed, breathing and heart function change to compensate for reduced oxygen transport.
Following chemoreception, the organism mounts ventilatory and cardiovascular adjustments. Santiago et al. showed that CO inhalation leads to increased ventilation and altered blood pressure in animal models. These responses are part of the broader physiological reaction to CO and are annotated under GO:0034465. The cardiovascular changes may include altered heart rate and vascular tone, although the exact mechanisms depend on the dose and duration of exposure.
Cellular Signaling and Gene Expression
In simple terms: At the cell level, CO triggers changes in gene activity and protein function, including anti-inflammatory and antioxidant pathways.
CO modulates intracellular signaling pathways, leading to changes in gene expression and enzyme activity. Hoetzel et al. reviewed that CO exerts anti-inflammatory effects in sepsis by modulating cytokine production and immune cell function. These effects are mediated in part by the activation of stress-responsive transcription factors and the inhibition of pro-inflammatory cascades. Stucki et al. further emphasized that CO can act as a signaling molecule affecting mitochondrial function and cell survival.
Erythropoietic and Neurovascular Responses
In simple terms: CO exposure can increase red blood cell production and alter brain blood flow signals.
CO exposure has been shown to transiently increase erythropoietin levels in females but not males, indicating sex-specific erythropoietic responses. Bendell et al. demonstrated that low-level CO exposure affects BOLD fMRI response, suggesting that CO influences neurovascular coupling. These responses are part of the systemic reaction to CO and are relevant to both physiological research and clinical imaging.
Retinal and Light-Dependent CO Dynamics
In simple terms: In the eye, light exposure changes carbon monoxide levels in retinal veins.
Oren et al. reported that retinal venous blood carbon monoxide responds to bright light in male pigs, indicating a link between light exposure and CO dynamics in the visual system. This finding expands the scope of GO:0034465 to include sensory organ responses and suggests that CO may play a role in retinal physiology. The mechanism may involve light-induced changes in heme oxygenase activity or blood flow.
Key Genes Involved in GO:0034465 response to carbon monoxide
The following genes and proteins have been implicated in the response to carbon monoxide based on the verified literature, though the list is not exhaustive and many annotations remain to be discovered.
| Gene | Major Role | Research Relevance |
|---|---|---|
| HMOX1 | Heme oxygenase 1 produces endogenous CO as a byproduct of heme degradation | Central to endogenous CO signaling and response to CO |
| HMOX2 | Heme oxygenase 2 generates CO in neurons and other tissues | Implicated in neurovascular and retinal CO responses |
| EPO | Erythropoietin is induced by CO exposure in a sex-dependent manner | Marker of erythropoietic response to CO |
| HIF1A | Hypoxia-inducible factor 1 alpha mediates cellular responses to low oxygen and CO | Potential regulator of gene expression changes during CO exposure |
| NFE2L2 | Nuclear factor erythroid 2 like 2 regulates antioxidant response elements | May mediate cytoprotective effects of low-dose CO |
| NFKB1 | Nuclear factor kappa B subunit 1 controls inflammatory gene expression | CO modulates NF-kB signaling in sepsis and inflammation |
| MAPK1 | Mitogen-activated protein kinase 1 transduces stress signals | Potential mediator of CO-induced signaling |
| MAPK3 | Mitogen-activated protein kinase 3 transduces stress signals | Potential mediator of CO-induced signaling |
| AKT1 | AKT serine/threonine kinase 1 promotes cell survival | May be activated by low-dose CO to protect cells |
| CASP3 | Caspase 3 executes apoptosis | CO can inhibit apoptosis in some contexts |
| BDNF | Brain-derived neurotrophic factor supports neuronal survival | May be modulated by CO in neurovascular responses |
| VEGFA | Vascular endothelial growth factor A regulates angiogenesis | Potential downstream target of CO signaling |
| NOS3 | Nitric oxide synthase 3 produces nitric oxide in endothelium | Interacts with CO in vascular regulation |
| NOS2 | Nitric oxide synthase 2 produces nitric oxide in inflammation | CO modulates inflammatory NO production |
| PTGS2 | Prostaglandin-endoperoxide synthase 2 is involved in inflammation | CO may alter prostaglandin synthesis |
| IL10 | Interleukin 10 is an anti-inflammatory cytokine | CO promotes anti-inflammatory IL-10 production |
| TNF | Tumor necrosis factor is a pro-inflammatory cytokine | CO suppresses TNF production in sepsis models |
| SLC11A2 | Divalent metal transporter 1 may influence heme iron availability | Potential role in CO sensing |
How Is response to carbon monoxide Regulated?
The response to carbon monoxide is regulated at multiple levels, including the availability of endogenous CO produced by heme oxygenases, the expression of CO-sensitive transcription factors such as HIF1A and NFE2L2, and the activity of inflammatory signaling cascades like NF-kB. Sex-specific regulation of erythropoietin induction by CO has been observed, suggesting hormonal modulation. Additionally, the microbiome can influence CO levels, as probiotic treatment altered CO in children with autism spectrum disorder. These regulatory layers ensure that the response to CO is context-dependent and tightly controlled.
response to carbon monoxide and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| HMOX1 | Sepsis and inflammation | HMOX1 knockout mice with CO exposure |
| EPO | Erythropoietic response to CO | EPO reporter knock-in cell line |
| NFKB1 | Inflammatory signaling in sepsis | NFKB1 knockout macrophages treated with CO |
| HIF1A | Hypoxic and CO signaling | HIF1A knockout cell lines under CO |
| BDNF | Neurovascular coupling | BDNF knockout neurons with CO exposure |
Carbon Monoxide Poisoning and Toxicology
Acute CO poisoning is a medical emergency that results from the same biological responses annotated under GO:0034465, including impaired oxygen transport and neurological damage. Understanding the ventilatory and cardiovascular responses to CO is essential for developing antidotes and supportive care. Stucki et al. reviewed that CO toxicity goes beyond simple hypoxia, involving mitochondrial dysfunction and inflammatory cascades.
Sepsis and Inflammatory Diseases
CO has been studied in sepsis for its anti-inflammatory properties, where low-dose CO can improve outcomes in animal models. Hoetzel et al. described that CO modulates cytokine production and immune cell function, making it a potential therapeutic agent. The response to CO in sepsis involves NF-kB and other inflammatory pathways.
Autism Spectrum Disorder and Neuroimmune Interactions
Sherman et al. found that CO levels correlate with symptom severity and autoimmunity in children with autism spectrum disorder, and that probiotic treatment alters CO levels. This suggests that the response to CO may be involved in neuroimmune crosstalk and could serve as a biomarker. The study was a post-hoc analysis of a randomized controlled trial, highlighting the need for further research.
Retinal and Visual Disorders
Oren et al. showed that retinal venous CO responds to bright light, indicating that CO dynamics in the eye may be relevant to visual physiology and potentially to retinal diseases. This finding links GO:0034465 to sensory organ function and suggests that CO could influence blood flow in the retina.
From response to carbon monoxide-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X mediate the ventilatory response to CO? | Knockout mouse with plethysmography |
| Does a point mutation in HMOX1 alter CO production? | Point-mutation knock-in cell line |
| Can a tagged CO sensor be visualized in live cells? | Tagged knock-in of candidate sensor |
| Does overexpression of EPO enhance CO-induced erythropoiesis? | Overexpression cell line or transgenic mouse |
| What genes are required for CO-induced anti-inflammatory effects? | CRISPR library screening in macrophages |
| Does CO alter BOLD fMRI signals in a specific brain region? | Knockout rat with fMRI |
How to Study the response to carbon monoxide Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Plethysmography | Ventilatory parameters | Assessing breathing response to CO |
| BOLD fMRI | Blood oxygenation changes | Neurovascular response to CO |
| RNA-seq | Global gene expression | Identifying CO-responsive genes |
| ELISA | Erythropoietin protein levels | Sex-specific erythropoietic response |
| Western blot | Protein expression and modifications | Validating signaling pathways |
| CRISPR library screening | Gene essentiality under CO | Discovering novel CO response genes |
| CO-releasing molecules | Localized CO delivery | Therapeutic and mechanistic studies |
| Probiotic intervention | Microbiome modulation of CO | Clinical studies in ASD |
Physiological Measurements
Ventilatory responses to CO can be measured using plethysmography in animal models, as demonstrated by Santiago et al.. Blood pressure and heart rate monitoring are also used to assess cardiovascular adjustments. These methods are essential for quantifying the organismal response to CO.
Imaging and Neurovascular Assessment
BOLD fMRI is used to measure changes in blood oxygenation in response to CO exposure, as shown by Bendell et al.. Retinal venous CO can be measured using spectrophotometric methods in animal models. These imaging techniques provide spatial and temporal resolution of CO responses.
Molecular and Cellular Assays
Gene expression changes in response to CO can be assessed by RNA-seq and qPCR. Protein levels and post-translational modifications are analyzed by Western blot and proteomics. Erythropoietin levels can be measured by ELISA.
Genetic and Pharmacological Manipulation
Knockout and knock-in models are used to test the role of specific genes in the CO response. CO-releasing molecules (CORMs) allow localized delivery of CO for mechanistic studies. Probiotic treatment can modulate CO levels, as shown in a clinical trial.
How CRISPR Can Be Used to Study GO:0034465 response to carbon monoxide
Knockout
CRISPR knockout of candidate genes such as HMOX1, HIF1A, or NFKB1 can determine their necessity in the response to carbon monoxide. For example, knocking out HMOX1 would reduce endogenous CO production and may blunt CO-responsive pathways. Knockout models are also useful for validating hits from library screens.
Point Mutation
Point mutations can be introduced to mimic disease-associated variants or to disrupt specific residues in CO-sensing proteins. For instance, mutating the heme-binding site of HMOX1 could alter its catalytic activity and CO production. These models help dissect the molecular determinants of CO recognition.
Knock-in
Knock-in of tagged versions of genes, such as HMOX1-GFP or EPO-luciferase, allows real-time monitoring of CO-induced expression and localization. Knock-in of reporter cassettes can also be used to screen for compounds that modulate the CO response.
Overexpression
Overexpression of genes like EPO or HMOX1 can enhance or amplify the response to CO, providing gain-of-function models. These models are useful for testing whether increased levels of a candidate gene are sufficient to alter CO sensitivity.
How EDITGENE Supports response to carbon monoxide Research
Researchers studying response to carbon monoxide-related genes often need to determine whether a candidate gene is causally involved in the response or merely correlated with it. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such causal studies, from knockout to overexpression and library screening.
Contact EDITGENE today to design your custom CRISPR model for response to carbon monoxide research.
Frequently Asked Questions About response to carbon monoxide
What is GO:0034465 response to carbon monoxide?
GO:0034465 is a Gene Ontology biological process term defined as any process that results in a change in state or activity of a cell or an organism as a result of a carbon monoxide (CO) stimulus.
What genes are involved in response to carbon monoxide?
Genes such as HMOX1, HMOX2, EPO, HIF1A, NFKB1, and NFE2L2 have been implicated in the response to CO.
How does carbon monoxide affect the body?
CO can cause toxicity at high doses but at low doses it acts as a signaling molecule affecting ventilation, inflammation, erythropoiesis, and neurovascular coupling.
What is the ventilatory response to carbon monoxide?
The ventilatory response to CO is a reflex increase in breathing mediated by the carotid body, as shown by Santiago et al..
Does carbon monoxide affect erythropoietin?
Yes, acute CO exposure transiently increases erythropoietin in females but not males, indicating sex-specific responses.
Can carbon monoxide be used therapeutically?
Low-dose CO and CO-releasing molecules are being explored for anti-inflammatory and cytoprotective effects in conditions like sepsis.
How is response to carbon monoxide studied?
It is studied using physiological measurements, imaging, molecular assays, and genetic models including knockout and knock-in.
What is the link between carbon monoxide and autism?
CO levels correlate with symptom severity and autoimmunity in children with autism spectrum disorder, and probiotics can alter CO levels.
Does light affect carbon monoxide in the eye?
Yes, retinal venous CO responds to bright light in male pigs, suggesting a role in visual physiology.
What CRISPR models are available for studying response to carbon monoxide?
EDITGENE offers knockout, point mutation, knock-in, overexpression, and library screening services for genes involved in the CO response.
Conclusion
GO:0034465 response to carbon monoxide is a broad biological process that encompasses physiological, cellular, and molecular changes triggered by CO. From ventilatory reflexes to gene expression and neurovascular effects, this term is central to understanding both CO toxicity and its potential therapeutic applications. Continued research using advanced CRISPR models and multi-omics approaches will further elucidate the mechanisms and identify new targets for intervention.
References
- 1. Bendell C et al.. 2020. Low-level carbon monoxide exposure affects BOLD fMRI response.. J Cereb Blood Flow Metab 40(11):2215-2224 PMID: 31711340
- 2. Stucki D et al.. 2020. Carbon monoxide - beyond toxicity?. Toxicol Lett 333:251-260 PMID: 32860873
- 3. DiMarco KG et al.. 2024. Acute exposure to carbon monoxide inhalation and/or hot water immersion transiently increases erythropoietin in females but not in males.. Exp Physiol 109(10):1782-1795 PMID: 39143855
- 4. Steiger C et al.. 2017. Localized delivery of carbon monoxide.. Eur J Pharm Biopharm 118:3-12 PMID: 27836646
- 5. Hoetzel A et al.. 2007. Carbon monoxide in sepsis.. Antioxid Redox Signal 9(11):2013-26 PMID: 17822362
- 6. Santiago TV et al.. 1976. Mechanism of the ventilatory response to carbon monoxide.. J Clin Invest 57(4):977-86 PMID: 947962
- 7. Sherman HT et al.. 2022. Carbon monoxide (CO) correlates with symptom severity, autoimmunity, and responses to probiotics treatment in a cohort of children with autism spectrum disorder (ASD): a post-hoc analysis of a randomized controlled trial.. BMC Psychiatry 22(1):536 PMID: 35941573
- 8. Oren DA et al.. 2017. Retinal venous blood carbon monoxide response to bright light in male pigs: A preliminary study.. J Photochem Photobiol B 168:12-15 PMID: 28135573
