ArticleProceedings of the National Academy of Sciences of the United States of America2022
NO rapidly mobilizes cellular heme to trigger assembly of its own receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- NO modulates human airway smooth muscle function by altering glucose-6-phosphate dehydrogenase effects on sGC function in asthma.Redox biology · 2026Article
- Heme-NO Dilates Arteries via Mobilization of NO Moieties From an Intracellular NO Store Within Vascular Smooth Muscle Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Regulatory interplay between nitric oxide and heme in redox signaling and inflammation.Redox biology · 2026Review
- Key roles of GAPDH, Hsp90, and NO in heme trafficking.Journal of inorganic biochemistry · 2026Review
- NO-cGMP Signaling in Endothelial Function of the Healthy and Inflamed Dental Pulp.International journal of molecular sciences · 2025Review
- Heme allocation in eukaryotic cells relies on mitochondrial heme export through FLVCR1b to cytosolic GAPDH.Nature communications · 2025Article
- The pivotal role of cytokines in liver disease pathogenesis and therapeutic potential.Frontiers in immunology · 2025Review
- The potential effect of natural antioxidants on endothelial dysfunction associated with arterial hypertension.Frontiers in cardiovascular medicine · 2024Review
- NO-ferroheme is a signaling entity in the vasculature.Nature chemical biology · 2023Article
- Negative regulation of biofilm formation by nitric oxide sensing proteins.Biochemical Society transactions · 2023Review
- NosP Detection of Heme ModulatesBiochemistry · 2023Article
- A natural heme deficiency exists in biology that allows nitric oxide to control heme protein functions by regulating cellular heme distribution.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- BAY58-2667 Activates Different Soluble Guanylyl Cyclase Species by Distinct Mechanisms that Indicate Its Principal Target in Cells is the Heme-Free Soluble Guanylyl Cyclase-Heat Shock Protein 90 Complex.Molecular pharmacology · 2023Article
- Cellular Factors That Shape the Activity or Function of Nitric Oxide-Stimulated Soluble Guanylyl Cyclase.Cells · 2023Review
- Thiol catalyzed formation of NO-ferroheme regulates canonical intravascular NO signaling.Research square · 2023Article
- Dental Pulp Inflammation Initiates the Occurrence of Mast Cells Expressing the αInternational journal of molecular sciences · 2023Article
- New roles for GAPDH, Hsp90, and NO in regulating heme allocation and hemeprotein function in mammals.Biological chemistry · 2022Review
- Article
- Endothelial Dysfunction in Acute Hepatic Porphyrias.Diagnostics (Basel, Switzerland) · 2022Article
- Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Nitric oxide (NO) signaling in biology relies on its activating cyclic guanosine monophosphate (cGMP) production by the NO receptor soluble guanylyl cyclase (sGC). sGC must obtain heme and form a heterodimer to become functional, but paradoxically often exists as an immature heme-free form in cells and tissues. Based on our previous finding that NO can drive sGC maturation, we investigated its basis by utilizing a fluorescent sGC construct whose heme level can be monitored in living cells. We found that NO generated at physiologic levels quickly triggered cells to mobilize heme to immature sGC. This occurred when NO was generated within cells or by neighboring cells, began within seconds of NO exposure, and led cells to construct sGC heterodimers and thus increase their active sGC level by several-fold. The NO-triggered heme deployment involved cellular glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-heme complexes and required the chaperone hsp90, and the newly formed sGC heterodimers remained functional long after NO generation had ceased. We conclude that NO at physiologic levels triggers assembly of its own receptor by causing a rapid deployment of cellular heme. Redirecting cellular heme in response to NO is a way for cells and tissues to modulate their cGMP signaling and to more generally tune their hemeprotein activities wherever NO biosynthesis takes place.
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Registered trials
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