GO:0030185 nitric oxide transport: Signaling Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0030185 nitric oxide transport describes the directed movement of nitric oxide (NO) into, out of, or within cells, often via transporters or pores [1,2].
• NO transport is critical for cardiovascular homeostasis, renal function, and host defense, with dysregulation linked to hypertension, atherosclerosis, and infection [3,5,4].
• Key proteins include hemoglobin, GST, MRP1, and L-arginine transporters, which facilitate NO storage, transport, and synthesis [2,3,7,8].
• Experimental models for studying NO transport include knockout mice, point-mutation cell lines, and CRISPR knock-in reporters [1,4,8].
• CRISPR screening and bioinformatics can identify novel regulators of NO transport and storage [2,6].
• Understanding NO transport mechanisms offers therapeutic targets for cardiovascular and infectious diseases [3,5,4].
Description
Nitric oxide (NO) is a gaseous signaling molecule involved in diverse physiological processes, including vasodilation, neurotransmission, and immune response. The Gene Ontology term GO:0030185, nitric oxide transport, encompasses the directed movement of NO into, out of, or within cells, often mediated by transporters or pores [1,2]. This process is essential for maintaining NO homeostasis and ensuring its availability for downstream signaling [3,5]. Dysregulated NO transport has been implicated in cardiovascular diseases, renal disorders, and microbial pathogenesis [3,5,4]. Researchers study NO transport to understand its role in health and disease, leveraging molecular and genetic tools to dissect the underlying mechanisms [6,7,8].
nitric oxide transport At A Glance
| GO ID | GO:0030185 |
|---|---|
| GO term | nitric oxide transport |
| Ontology | biological_process |
| Synonym | none |
| Major function | Directed movement of nitric oxide across membranes or within cells |
| Related cellular components | Plasma membrane, hemoglobin complex, multidrug resistance-associated protein 1 (MRP1) |
| Related molecular functions | Nitric oxide binding, transporter activity, glutathione transferase activity |
| Associated diseases | Cardiovascular disease, renal dysfunction, bacterial infection |
| Key regulators | L-arginine transporters, glutathione-S-transferase, MRP1, hemoglobin |
What Is GO:0030185?
GO:0030185 nitric oxide transport is defined as the directed movement of nitric oxide (nitrogen monoxide) into, out of, or within a cell, or between cells, by means of some agent such as a transporter or pore. This biological process ensures that NO, a short-lived free radical, reaches its targets and is appropriately stored or scavenged, influencing signaling and cellular responses [1,2,3].
Why Is nitric oxide transport Important in Cell Biology?
Nitric oxide transport is fundamental to cardiovascular health, as it regulates vasodilation and blood flow, and to renal function by modulating tubular transport [1,5]. In the immune system, NO transport influences host defense against pathogens, and its dysregulation contributes to disease pathogenesis [4,6]. Understanding NO transport mechanisms can reveal therapeutic targets for hypertension, atherosclerosis, and infectious diseases [3,5,4].
• Regulates vasodilation and blood pressure through endothelial NO signaling [3,8].
• Modulates renal sodium and water transport, affecting fluid balance [1,5].
• Facilitates NO storage in erythrocytes via hemoglobin and glutathione conjugates [2,7].
• Plays a role in host defense against bacterial infections, as seen in Staphylococcus aureus NO resistance.
• Involves iron-nitrosyl complex transport, linking NO to iron metabolism.
• Dysregulation is linked to cardiovascular diseases such as atherosclerosis and hypertension.
• Impacts endothelial progenitor cell function and angiogenesis.
• Provides targets for pharmacological modulation of NO availability [2,6].
• Essential for understanding NO-mediated signaling in diverse cell types [1,5].
• CRISPR-based models enable precise dissection of NO transport genes [4,8].
What Happens During nitric oxide transport?
NO Synthesis and Intracellular Availability
In simple terms: NO is made inside cells from L-arginine, and its transport starts with its production.
Nitric oxide is synthesized by nitric oxide synthases (NOS) from L-arginine. In endothelial progenitor cells, L-arginine transport is a rate-limiting step for NO synthesis, linking transport processes to NO production. This intracellular NO can then diffuse or be transported to target sites.
Transport Across Membranes
In simple terms: NO moves across cell membranes with the help of specific proteins.
NO transport across plasma membranes can occur via diffusion, but facilitated transport by proteins such as multidrug resistance-associated protein 1 (MRP1) and glutathione-S-transferase (GST) has been described. These proteins may transport NO or its metabolites, influencing cellular NO levels. In erythrocytes, the plasma membrane plays a role in transporting NO, oxygen, and carbon dioxide, maintaining heme iron in a reduced state.
Intracellular Storage and Buffering
In simple terms: Inside cells, NO can be stored by binding to proteins, which controls its availability.
NO can be stored as dinitrosyl iron complexes (DNICs) with iron and thiols, and transported within cells. Hemoglobin in erythrocytes can bind NO, forming iron-nitrosyl complexes that serve as a reservoir [3,7]. Glutathione-S-transferase and MRP1 are also implicated in NO storage and transport, affecting NO bioavailability.
Intercellular Transfer and Signaling
In simple terms: NO can move between cells to deliver signals.
NO transport between cells, such as from endothelium to smooth muscle, is crucial for vasodilation. In the kidney, NO produced in one cell type can affect transport in neighboring tubules, as seen in thick ascending limb regulation. This intercellular transfer often involves diffusion or transporter-mediated mechanisms [1,3].
Regulation of NO Transport
In simple terms: The movement of NO is controlled by various factors, including substrate availability and protein interactions.
NO transport is regulated by L-arginine availability, expression of transporters like MRP1, and the presence of storage proteins [2,8]. In renal proximal tubules, NO modulates Na+ transport, and its own transport may be influenced by local factors. Bacterial NO resistance involves specialized phosphate transport, highlighting diverse regulatory mechanisms.
Key Genes Involved in GO:0030185 nitric oxide transport
The following genes and proteins are key players in nitric oxide transport, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| NOS3 | Endothelial nitric oxide synthase; produces NO | Studied for vascular function and NO synthesis |
| SLC7A1 | L-arginine transporter; supplies substrate for NO synthesis | Rate-limiting for NO production in endothelial progenitor cells |
| ABCC1 | Multidrug resistance-associated protein 1; transports NO metabolites | Involved in NO transport and storage |
| GST | Glutathione-S-transferase; conjugates NO and facilitates transport | Linked to NO storage and transport |
| HBB | Hemoglobin beta; binds and transports NO | NO transport and storage in erythrocytes [3,7] |
| HBA1 | Hemoglobin alpha; binds and transports NO | NO transport and storage in erythrocytes [3,7] |
| SLC7A2 | Cationic amino acid transporter; L-arginine transport | Potential role in NO synthesis |
| SLC3A2 | Chaperone for L-arginine transporters | Supports L-arginine transport for NO synthesis |
| ALB | Albumin; may carry NO or NO adducts | NO transport in plasma |
| GCLC | Glutamate-cysteine ligase; glutathione synthesis | Affects NO storage via glutathione |
| GCLM | Glutamate-cysteine ligase modifier; glutathione synthesis | Affects NO storage via glutathione |
| NCF1 | Neutrophil cytosolic factor 1; involved in NO signaling | Potential role in NO transport in immune cells |
| SLC17A1 | Phosphate transporter; NO resistance in bacteria | Essential for Staphylococcus aureus NO resistance |
| SLC17A2 | Phosphate transporter; NO resistance in bacteria | Essential for Staphylococcus aureus NO resistance |
| SLC17A3 | Phosphate transporter; NO resistance in bacteria | Essential for Staphylococcus aureus NO resistance |
| SLC17A4 | Phosphate transporter; NO resistance in bacteria | Essential for Staphylococcus aureus NO resistance |
| DMT1 | Divalent metal transporter 1; iron transport | Iron transport linked to NO storage |
| FPN1 | Ferroportin; iron export | Iron export linked to NO storage |
How Is nitric oxide transport Regulated?
Nitric oxide transport is regulated at multiple levels. L-arginine transport via cationic amino acid transporters (CATs) controls substrate availability for NO synthesis, as shown in endothelial progenitor cells. The expression and activity of MRP1 and GST influence NO storage and transport. In the kidney, NO transport and signaling are modulated by local factors, affecting tubular transport [1,5]. Additionally, iron metabolism and the formation of dinitrosyl iron complexes regulate NO storage and transport. Bacterial NO resistance requires specialized phosphate transport, indicating diverse regulatory mechanisms.
nitric oxide transport and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| NOS3 | Cardiovascular disease, hypertension | Knockout mouse, endothelial cell line |
| ABCC1 | NO transport and storage, drug resistance | Knockout cell line, overexpression |
| GST | NO storage, oxidative stress | Point mutation, knockout |
| HBB | Sickle cell disease, NO transport | Knock-in mouse, erythroid cells |
| SLC17A1 | Staphylococcus aureus NO resistance | Bacterial knockout |
Cardiovascular Disease
Impaired NO transport and bioavailability contribute to endothelial dysfunction, hypertension, and atherosclerosis. Hemoglobin-mediated NO transport in erythrocytes is critical for cardiovascular homeostasis, and alterations in this process can lead to disease [3,7]. L-arginine transport defects in endothelial progenitor cells may impair angiogenesis and vascular repair.
Renal Dysfunction
NO transport modulates renal tubular transport, particularly in the proximal tubule and thick ascending limb. Dysregulation of NO transport can affect sodium and water reabsorption, contributing to hypertension and kidney disease [1,5].
Infectious Diseases
Bacterial pathogens like Staphylococcus aureus require specialized phosphate transport for NO resistance, which is essential for survival within host cells. Targeting NO transport mechanisms could combat infections.
Iron Metabolism Disorders
NO transport and storage are intertwined with iron metabolism through dinitrosyl iron complexes. Disruption of this interplay may contribute to iron-related disorders.
From nitric oxide transport-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does NOS3 knockout affect NO transport? | NOS3 knockout mouse or endothelial cell line |
| How does MRP1 regulate NO storage? | ABCC1 knockout or overexpression cell line |
| What is the role of GST in NO transport? | GST point mutation or knockout cells |
| Can we visualize NO transport in real time? | Knock-in fluorescent NO reporter cells |
| Does SLC17A1 mediate bacterial NO resistance? | SLC17A1 knockout Staphylococcus aureus |
| How does hemoglobin transport NO? | HBB knock-in mouse with modified NO binding |
How to Study the nitric oxide transport Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Gene function in NO transport | Identify essential genes [2,4] |
| Fluorescent NO probes | Intracellular NO levels and transport | Live-cell imaging |
| EPR spectroscopy | Dinitrosyl iron complexes | NO storage quantification |
| Nitrite/nitrate assay | NO production and transport | Cell culture and plasma |
| RNA-seq | Transcriptional changes in NO transport genes | Pathway analysis |
| Proteomics | Protein interactions in NO transport | Identify novel transporters |
| CRISPR screen | Genome-wide regulators of NO resistance | Bacterial and mammalian cells |
| Knock-in reporters | Real-time NO dynamics | Visualize transport in vivo |
Genetic Knockout and Knockdown
CRISPR-Cas9 knockout or RNA interference can deplete genes involved in NO transport, such as ABCC1 or GST, to assess their impact on NO storage and transport. Knockout mice for NOS3 have been used to study NO synthesis and transport in vivo.
Fluorescent and Luminescent NO Detection
NO-sensitive fluorescent probes (e.g., DAF-FM) allow real-time imaging of NO transport and distribution in live cells. These methods can be combined with genetic manipulation to study transport mechanisms.
Biochemical Assays for NO Metabolites
Measurement of nitrite/nitrate (NOx) and dinitrosyl iron complexes by electron paramagnetic resonance (EPR) or colorimetric assays quantifies NO transport and storage.
CRISPR Library Screening
Genome-wide CRISPR screens can identify novel regulators of NO transport and resistance. For example, screening in Staphylococcus aureus under NO stress revealed phosphate transporters essential for resistance.
How CRISPR Can Be Used to Study GO:0030185 nitric oxide transport
Knockout
CRISPR knockout of genes like ABCC1 or GST can abolish NO transport and storage, revealing their roles in cellular NO homeostasis. Knockout of SLC17A1 in Staphylococcus aureus demonstrated its essentiality for NO resistance.
Point Mutation
Introducing point mutations in genes such as HBB can alter NO binding and transport, mimicking disease-associated variants. Point mutations in GST can dissect its catalytic role in NO storage.
Knock-in
Knock-in of fluorescent tags or reporter genes into loci like NOS3 allows real-time tracking of NO synthesis and transport. Knock-in of disease mutations in HBB can model sickle cell disease and its impact on NO transport.
Overexpression
Overexpression of MRP1 or GST can enhance NO transport and storage, providing gain-of-function models to study NO bioavailability. Overexpression of L-arginine transporters can boost NO synthesis in endothelial cells.
How EDITGENE Supports nitric oxide transport Research
Researchers studying nitric oxide transport-related genes often need to determine whether a candidate gene is causally involved in NO movement, storage, or signaling. EDITGENE provides a comprehensive suite of CRISPR services to generate precisely engineered cell and animal models, enabling functional validation of genes implicated in GO:0030185.
Contact EDITGENE today to design your custom CRISPR model for nitric oxide transport research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EDN1 Knockout HEK293 Cell Line | EDJ-KQ1485 | Human | 1906 | Details Get a Quote |
| HBB Knockout HEK293 Cell Line | EDJ-KQ3886 | Human | 3043 | Details Get a Quote |
| EDN1 Knockout A-549 Cell Line | EDJ-KQ21075 | Human | 1906 | Details Get a Quote |
| EDN1 Knockout HCT 116 Cell Line | EDJ-KQ21076 | Human | 1906 | Details Get a Quote |
| EDN1 Knockout HeLa Cell Line | EDJ-KQ21077 | Human | 1906 | Details Get a Quote |
| AQP1 Knockout HEK293 Cell Line | EDJ-KQ50127 | Human | 358 | Details Get a Quote |
| HBA1 Knockout HEK293 Cell Line | EDJ-KQ50340 | Human | 3039 | Details Get a Quote |
| HBA2 Knockout HEK293 Cell Line | EDJ-KQ50341 | Human | 3040 | Details Get a Quote |
| AQP1 Knockout HeLa Cell Line | EDJ-KQ52644 | Human | 358 | Details Get a Quote |
| HBA1 Knockout HeLa Cell Line | EDJ-KQ53492 | Human | 3039 | Details Get a Quote |
| HBA2 Knockout HeLa Cell Line | EDJ-KQ53493 | Human | 3040 | Details Get a Quote |
| HBB Knockout HeLa Cell Line | EDJ-KQ53495 | Human | 3043 | Details Get a Quote |
| AQP1 Knockout A-549 Cell Line | EDJ-KQ61117 | Human | 358 | Details Get a Quote |
| HBA1 Knockout A-549 Cell Line | EDJ-KQ61963 | Human | 3039 | Details Get a Quote |
| HBA2 Knockout A-549 Cell Line | EDJ-KQ61964 | Human | 3040 | Details Get a Quote |
Displaying Records 1 To 15 Of 20 Records
Frequently Asked Questions About nitric oxide transport
What is nitric oxide transport?
Nitric oxide transport (GO:0030185) is the directed movement of nitric oxide into, out of, or within cells, often via transporters or pores [1,2].
What genes are involved in nitric oxide transport?
Key genes include NOS3, ABCC1, GST, HBB, and SLC17A1, among others [2,3,4,8].
How is nitric oxide transported in the blood?
In blood, NO is transported by hemoglobin and albumin, and stored as iron-nitrosyl complexes [3,7].
What is the role of MRP1 in nitric oxide transport?
MRP1 (ABCC1) transports NO metabolites and contributes to NO storage and bioavailability.
How does nitric oxide affect renal transport?
NO modulates sodium and water transport in the kidney, influencing blood pressure and fluid balance [1,5].
Can CRISPR be used to study nitric oxide transport?
Yes, CRISPR knockout, knock-in, and point mutations enable precise dissection of NO transport genes [2,4,7].
What diseases are linked to nitric oxide transport?
Cardiovascular disease, renal dysfunction, and bacterial infections are associated with altered NO transport [3,4,5].
How is nitric oxide stored in cells?
NO can be stored as dinitrosyl iron complexes or bound to glutathione and hemoglobin [2,6].
What methods measure nitric oxide transport?
Fluorescent probes, EPR, nitrite/nitrate assays, and CRISPR screens are commonly used [3,4,6].
Why is nitric oxide transport important for immunity?
NO transport affects host defense, and pathogens like Staphylococcus aureus require specialized transport for NO resistance.
Conclusion
Nitric oxide transport (GO:0030185) is a vital biological process that ensures NO reaches its targets and is appropriately stored, impacting cardiovascular, renal, and immune functions. Dysregulation contributes to major diseases, making it a key area of research. Advances in CRISPR technology and bioinformatics are accelerating the discovery of novel regulators and therapeutic targets in NO transport [2,3,4,6].
References
- 1. Satoh N et al.. 2017. Effects of Nitric Oxide on Renal Proximal Tubular Na(+) Transport.. Biomed Res Int 2017:6871081 PMID: 29181400
- 2. Russell TM et al.. 2021. The Relationship of Glutathione-S-Transferase and Multi-Drug Resistance-Related Protein 1 in Nitric Oxide (NO) Transport and Storage.. Molecules 26(19) PMID: 34641326
- 3. Muller B et al.. 2002. Nitric oxide transport and storage in the cardiovascular system.. Ann N Y Acad Sci 962:131-9 PMID: 12076970
- 4. Stephens AC et al.. 2023. Specialized phosphate transport is essential for Staphylococcus aureus nitric oxide resistance.. mBio 14(6):e0245123 PMID: 37937971
- 5. Herrera M et al.. 2006. Regulation of thick ascending limb transport: role of nitric oxide.. Am J Physiol Renal Physiol 290(6):F1279-84 PMID: 16682483
- 6. Richardson DR et al.. 2008. The nitric oxide-iron interplay in mammalian cells: transport and storage of dinitrosyl iron complexes.. Biochim Biophys Acta 1780(4):638-51 PMID: 18206118
- 7. De Rosa MC et al.. 2007. The plasma membrane of erythrocytes plays a fundamental role in the transport of oxygen, carbon dioxide and nitric oxide and in the maintenance of the reduced state of the heme iron.. Gene 398(1-2):162-71 PMID: 17573207
- 8. Díaz-Pérez F et al.. 2012. L-arginine transport and nitric oxide synthesis in human endothelial progenitor cells.. J Cardiovasc Pharmacol 60(5):439-49 PMID: 23143655
