GO:1904880 response to hydrogen sulfide: Signaling Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1904880 (response to hydrogen sulfide) describes any process that changes a cell or organism's state or activity in response to hydrogen sulfide (H2S).
• Hydrogen sulfide is a gaseous signaling molecule that modulates enzyme production, gene expression, movement, and secretion in both plants and animals.
• In plants, H2S signaling is central to abiotic stress responses, including oxidative stress, low-light stress, and photosynthesis regulation.
• In mammals, H2S influences inflammation, immune responses, vasoplegic shock pathophysiology, and antioxidant defense.
• H2S production can be modulated by diet and by activatable small-molecule donors, making it a tractable experimental target.
• CRISPR-based knockout, knock-in, point-mutation, and overexpression models are key tools for dissecting genes involved in response to hydrogen sulfide.
Description
Hydrogen sulfide (H2S) is a gaseous signaling molecule that elicits a broad range of cellular and organismal responses. The Gene Ontology term GO:1904880, response to hydrogen sulfide, captures any process that results in a change in state or activity of a cell or an organism as a result of an H2S stimulus. This includes changes in movement, secretion, enzyme production, and gene expression. The term is synonymous with response to dihydridosulfur and response to sulfane, reflecting the chemical diversity of H2S-related stimuli. Understanding this response is critical because H2S is now recognized as a key mediator in both plant stress physiology and mammalian pathophysiology. In plants, H2S signaling intersects with reactive oxygen species (ROS) crosstalk and regulates photosynthesis under low-light stress. In mammals, H2S is implicated in vasoplegic shock, inflammation, and immune modulation. The breadth of these roles makes GO:1904880 a focal point for researchers studying redox biology, signal transduction, and stress adaptation.
response to hydrogen sulfide At A Glance
| GO ID | GO:1904880 |
|---|---|
| GO term | response to hydrogen sulfide |
| Ontology | biological_process |
| Synonym | response to dihydridosulfur; response to sulfane |
| Definition | Any process that results in a change in state or activity of a cell or an organism as a result of a hydrogen sulfide stimulus. |
| Major function | Mediates cellular and organismal adaptation to H2S, including changes in gene expression, enzyme activity, and redox balance. |
| Taxonomic scope | Observed in plants, mammals, and other organisms. |
| Related stimuli | Hydrogen sulfide (H2S), dihydridosulfur, sulfane sulfur species. |
| Research relevance | Central to understanding stress responses, inflammation, vasoplegia, and antioxidant defense. |
What Is GO:1904880?
According to the QuickGO definition, GO:1904880 (response to hydrogen sulfide) is 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 hydrogen sulfide stimulus. This biological process term encompasses the downstream signaling, metabolic, and transcriptional changes triggered when cells encounter H2S or its related species such as sulfane sulfur. The response can be adaptive, protective, or pathological depending on context, and it is observed across taxa from plants to humans.
Why Is response to hydrogen sulfide Important in Cell Biology?
GO:1904880 is important because hydrogen sulfide is a pleiotropic signaling molecule with roles in both normal physiology and disease. In plants, H2S improves photosynthesis under low-light stress and participates in oxidative stress responses through crosstalk with ROS. In mammals, H2S is a key mediator of vasoplegic shock and inflammation, and H2S donors are being developed as therapeutic agents. The response to H2S also intersects with diet, as differential H2S production has been observed in human cohorts in response to animal- and plant-based diets. Understanding this process at the molecular level can inform therapeutic strategies and agricultural interventions.
• H2S is a gaseous signaling molecule that regulates vasodilation and vascular tone, with implications for vasoplegic shock.
• H2S donors are being developed as anti-inflammatory and immune-modulating therapeutics.
• In plants, H2S signaling enhances tolerance to abiotic stresses such as low light and oxidative stress.
• H2S crosstalk with reactive oxygen species (ROS) is critical for redox homeostasis.
• Dietary interventions can alter endogenous H2S production in humans.
• Activatable small-molecule H2S donors enable precise temporal control of H2S release for research.
• Tandem biocatalysis can generate H2S to promote endogenous antioxidant responses.
• Dysregulation of H2S signaling is linked to inflammation and immune dysfunction.
• H2S modulates enzyme production and gene expression, affecting multiple metabolic pathways.
• Understanding H2S response mechanisms can guide CRISPR-based functional genomics screens.
What Happens During response to hydrogen sulfide?
H2S Perception and Chemical Reactivity
In simple terms: Cells first sense the presence of hydrogen sulfide, which can react with proteins and small molecules.
The response to hydrogen sulfide begins with the perception of H2S or its related species such as sulfane sulfur. H2S is a small, diffusible gas that can permeate membranes and react with metal centers, thiols, and disulfide bonds in proteins. This reactivity underlies its ability to modify enzyme activity and trigger signaling cascades. In plants, H2S is produced endogenously and can also be applied exogenously to study responses. The chemical nature of H2S donors, including activatable small molecules, allows researchers to control its release and study downstream effects.
Redox and ROS Crosstalk
In simple terms: Hydrogen sulfide interacts with reactive oxygen species to balance cellular oxidation and reduction.
A major component of the response to H2S is its crosstalk with reactive oxygen species (ROS). H2S can act as an antioxidant by scavenging ROS or by enhancing antioxidant enzyme activity, but it can also modulate ROS production. In plants, this crosstalk is essential for oxidative stress responses and is integrated with other stress signaling pathways. The balance between H2S and ROS influences whether the response is protective or damaging, depending on concentration and context.
Transcriptional and Translational Changes
In simple terms: Cells change which genes are turned on or off in response to hydrogen sulfide.
Exposure to H2S leads to changes in gene expression, including upregulation of antioxidant genes and stress-responsive transcription factors. In plants, H2S signaling regulates chlorophyll and carotenoid metabolisms, affecting photosynthesis-related gene expression. In mammals, H2S modulates inflammatory and immune gene programs. These transcriptional changes are part of the cellular adaptation to H2S and are often mediated by redox-sensitive transcription factors.
Physiological and Metabolic Outcomes
In simple terms: The response ultimately changes how cells and organisms function, from photosynthesis to vascular tone.
The downstream outcomes of H2S response include altered enzyme production, secretion, and movement. In plants, H2S improves photosynthesis under low-light stress by regulating chlorophyll and carotenoid metabolisms. In mammals, H2S influences vascular smooth muscle relaxation and can contribute to vasoplegic shock. H2S also promotes endogenous antioxidant responses through tandem biocatalysis. These physiological outcomes are the ultimate manifestation of GO:1904880.
Key Genes Involved in GO:1904880 response to hydrogen sulfide
The following genes and proteins are experimentally implicated in the response to hydrogen sulfide across plant and mammalian systems.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CBS | Cystathionine beta-synthase, an H2S-producing enzyme | Studied in vasoplegic shock and H2S production |
| CSE | Cystathionine gamma-lyase, an H2S-producing enzyme | Involved in vascular H2S signaling |
| MPST | Mercaptopyruvate sulfurtransferase, H2S generation | Contributes to H2S production in tissues |
| CAT | Catalase, antioxidant enzyme | Modulated by H2S in oxidative stress responses |
| SOD | Superoxide dismutase, antioxidant enzyme | Interacts with H2S in ROS crosstalk |
| APX | Ascorbate peroxidase, plant antioxidant enzyme | Part of H2S-mediated oxidative stress response |
| NR | Nitrate reductase, plant enzyme | Linked to H2S signaling in plants |
| LCD | L-cysteine desulfhydrase, plant H2S-producing enzyme | Key for H2S generation in plant stress responses |
| DCD | D-cysteine desulfhydrase, plant H2S-producing enzyme | Contributes to H2S production in plants |
| PSII | Photosystem II, photosynthesis component | Regulated by H2S under low-light stress |
| Chl | Chlorophyll biosynthesis enzymes | Modulated by H2S to improve photosynthesis |
| Car | Carotenoid biosynthesis enzymes | Regulated by H2S in stress responses |
| NF-kB | Inflammatory transcription factor | Modulated by H2S donors in inflammation |
| Nrf2 | Antioxidant response transcription factor | Activated by H2S to promote antioxidant genes |
| IL-6 | Pro-inflammatory cytokine | Influenced by H2S in immune responses |
| TNF-alpha | Pro-inflammatory cytokine | Regulated by H2S in inflammation |
| HIF-1alpha | Hypoxia-inducible factor | Potential crosstalk with H2S signaling |
How Is response to hydrogen sulfide Regulated?
The response to hydrogen sulfide is regulated at multiple levels. H2S production is controlled by the activity of H2S-generating enzymes such as CBS, CSE, and MPST, which can be modulated by diet and metabolic state. Exogenous H2S donors, including activatable small molecules, allow temporal control of H2S release and downstream signaling. In plants, H2S signaling is integrated with ROS and nitric oxide pathways, and is regulated by stress conditions such as low light and oxidative stress. Transcriptional regulation of antioxidant and inflammatory genes further shapes the response.
response to hydrogen sulfide and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CBS | Vasoplegic shock | Knockout mouse or endothelial cell model |
| CSE | Vascular dysfunction | Knockout or overexpression in vascular smooth muscle cells |
| NF-kB | Inflammation | Reporter cell line with H2S donor treatment |
| Nrf2 | Oxidative stress | Knockout or knock-in in mammalian cells |
| LCD | Plant abiotic stress | Arabidopsis knockout or overexpression |
Vasoplegic Shock and Vascular Dysfunction
Hydrogen sulfide is a key mediator of vasoplegic shock, a condition characterized by severe hypotension and vascular hyporesponsiveness. H2S produced by CBS and CSE contributes to vasodilation and is implicated in the pathophysiology of vasoplegic shock. Understanding the response to H2S in vascular cells is therefore critical for developing therapeutic strategies.
Inflammation and Immune Dysregulation
H2S plays a dual role in inflammation, with both pro- and anti-inflammatory effects depending on context. H2S donors have been explored as therapeutic approaches in inflammation and immune response, modulating cytokines such as IL-6 and TNF-alpha. The response to H2S in immune cells is therefore a target for anti-inflammatory drug development.
Oxidative Stress-Related Diseases
Because H2S crosstalks with ROS, dysregulation of H2S signaling is linked to oxidative stress-related pathologies. In plants, H2S improves oxidative stress tolerance, and in mammals, H2S promotes endogenous antioxidant responses. This makes the response to H2S relevant to diseases involving oxidative damage, such as cardiovascular and neurodegenerative conditions.
From response to hydrogen sulfide-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X mediate H2S-induced antioxidant response? | CRISPR knockout in mammalian cell line |
| Does point mutation in CBS alter H2S production? | Point-mutation knock-in in cell line |
| Does overexpression of CSE enhance H2S signaling? | Overexpression cell model |
| Does H2S regulate photosynthesis genes? | Plant knockout or overexpression |
| Does H2S donor affect inflammatory gene expression? | Reporter knock-in or RNA-seq |
| Does diet alter H2S production? | Human cohort study with dietary intervention |
How to Study the response to hydrogen sulfide Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global gene expression changes | Identify H2S-responsive transcripts |
| Redox proteomics | Cysteine modifications (persulfidation) | Detect H2S-target proteins |
| H2S fluorescent probes | Intracellular H2S levels | Monitor H2S dynamics |
| CRISPR knockout screen | Gene essentiality for H2S response | Discover novel regulators |
| Western blot | Protein expression and modification | Validate H2S effects on specific proteins |
| Photosynthesis assays | Chlorophyll fluorescence and carotenoid content | Assess H2S effects in plants |
| Dietary intervention study | Endogenous H2S production | Link diet to H2S response |
RNA Sequencing (RNA-seq)
RNA-seq is used to profile global gene expression changes in response to H2S. This method can identify transcriptional programs activated by H2S donors or endogenous H2S production. In plants, RNA-seq has revealed H2S-regulated genes involved in photosynthesis and stress responses.
Proteomics and Redox Proteomics
Proteomic approaches can identify proteins modified by H2S, such as through persulfidation. Redox proteomics specifically detects cysteine modifications induced by H2S, linking the response to enzyme activity changes.
H2S Measurement and Donor Assays
Quantifying H2S production and release is essential. Methods include colorimetric assays, fluorescent probes, and the use of activatable small-molecule donors to control H2S delivery. These tools enable precise dose-response studies.
CRISPR Screening
Genome-wide CRISPR knockout or activation screens can identify genes required for the response to H2S. Such screens are powerful for uncovering novel regulators of H2S signaling and antioxidant responses.
How CRISPR Can Be Used to Study GO:1904880 response to hydrogen sulfide
Knockout
CRISPR knockout of H2S-producing enzymes such as CBS or CSE can abolish endogenous H2S production, allowing researchers to study the contribution of specific genes to the response to hydrogen sulfide. Knockout models are also used to identify genes required for H2S-induced antioxidant responses.
Point Mutation
Point mutations can be introduced into genes encoding H2S-metabolizing enzymes to mimic disease-associated variants or to dissect catalytic residues. For example, point mutations in CBS can alter H2S production and affect vascular function.
Knock-in
Knock-in of reporter genes or tags into H2S-responsive loci enables real-time monitoring of gene expression or protein localization. Tagged knock-in of antioxidant genes can reveal their dynamics under H2S treatment.
Overexpression
Overexpression of H2S-generating enzymes or antioxidant genes can enhance the response to H2S and protect against oxidative stress. Overexpression models are useful for gain-of-function studies in both plant and mammalian systems.
How EDITGENE Supports response to hydrogen sulfide Research
Researchers studying response to hydrogen sulfide-related genes often need to determine whether a candidate gene is causally involved in H2S sensing, metabolism, or downstream signaling. CRISPR-based genome editing provides a precise way to test these hypotheses by creating knockout, point-mutation, knock-in, and overexpression models. EDITGENE offers a comprehensive suite of services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for response to hydrogen sulfide research.
Frequently Asked Questions About response to hydrogen sulfide
What is GO:1904880?
GO:1904880 is the Gene Ontology term for response to hydrogen sulfide, defined as any process that results in a change in state or activity of a cell or an organism as a result of a hydrogen sulfide stimulus.
What genes are involved in response to hydrogen sulfide?
Key genes include CBS, CSE, MPST, and antioxidant genes such as CAT and SOD in mammals, and LCD, DCD, and NR in plants.
How does hydrogen sulfide affect cells?
H2S can modify proteins, crosstalk with ROS, and alter gene expression, leading to changes in enzyme production, secretion, and movement.
What diseases are linked to hydrogen sulfide signaling?
H2S is linked to vasoplegic shock, inflammation, and oxidative stress-related diseases.
How can I study response to hydrogen sulfide using CRISPR?
CRISPR knockout, point mutation, knock-in, and overexpression models can be used to test gene function in H2S response.
What are the synonyms for response to hydrogen sulfide?
The synonyms are response to dihydridosulfur and response to sulfane.
Is hydrogen sulfide a signaling molecule?
Yes, H2S is a gaseous signaling molecule involved in vasodilation, inflammation, and antioxidant defense.
How is H2S produced in the body?
H2S is produced by enzymes such as CBS, CSE, and MPST, and production can be influenced by diet.
What is the role of H2S in plants?
In plants, H2S improves photosynthesis under low-light stress and participates in oxidative stress responses.
What methods are used to study H2S response?
Methods include RNA-seq, redox proteomics, H2S fluorescent probes, and CRISPR screens.
Conclusion
GO:1904880 (response to hydrogen sulfide) is a fundamental biological process that mediates cellular and organismal adaptation to H2S. Its roles span plant stress physiology and mammalian pathophysiology, including vasoplegic shock, inflammation, and oxidative stress. CRISPR-based models are indispensable for dissecting the genes and mechanisms underlying this response. As H2S-based therapeutics advance, understanding this process will remain a high-priority research area.
References
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- 2. Manna S et al.. 2025. Tandem Biocatalysis to Generate Hydrogen Sulfide and Promote Endogenous Antioxidant Response.. Angew Chem Int Ed Engl 64(24):e202502917 PMID: 40170193
- 3. Zhao R et al.. 2022. Hydrogen sulphide signalling in plant response to abiotic stress.. Plant Biol (Stuttg) 24(4):523-531 PMID: 34837449
- 4. Liu Z et al.. 2024. Hydrogen Sulfide in the Oxidative Stress Response of Plants: Crosstalk with Reactive Oxygen Species.. Int J Mol Sci 25(3) PMID: 38339212
- 5. Levinn CM et al.. 2020. Activatable Small-Molecule Hydrogen Sulfide Donors.. Antioxid Redox Signal 32(2):96-109 PMID: 31554416
- 6. Teigen L et al.. 2022. Differential hydrogen sulfide production by a human cohort in response to animal- and plant-based diet interventions.. Clin Nutr 41(6):1153-1162 PMID: 35500315
- 7. Li M et al.. 2021. New Therapeutic Approaches Using Hydrogen Sulfide Donors in Inflammation and Immune Response.. Antioxid Redox Signal 35(5):341-356 PMID: 33789440
- 8. Liu B et al.. 2022. Hydrogen sulfide improves tall fescue photosynthesis response to low-light stress by regulating chlorophyll and carotenoid metabolisms.. Plant Physiol Biochem 170:133-145 PMID: 34883320
