Revisiting Nitric Oxide Signaling: Where Was It, and Where Is It Going?

Marletta, Michael A.

doi:10.1021/acs.biochem.1c00276

Cited by 13 publications

(7 citation statements)

References 43 publications

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“…cGMP is the second messenger molecule and activates cGMP‐dependent serine/threonine protein kinase (PKG) which then modulates various cell processes including cardio‐protection (from both reactive hypertrophy and reperfusion injury), inflammatory responses, phagocytic defense mechanisms, inhibition of platelet aggregation, vasodilation, neurotransmission, and calcium homeostasis. [ 38 ] cGMP is hydrolyzed into an inactive 5′‐GMP metabolite by the phosphodiesterase enzyme. A balance between the levels of soluble guanylate cyclase and inhibitory phosphodiesterase determines the levels of cGMP.…”

Section: No Production Signaling and Roles In Human Physiology And Di...mentioning

confidence: 99%

Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications

Andrabi,

Sharma,

Karan

et al. 2023

Advanced Science

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Nitric oxide (NO) is a gaseous molecule that has a central role in signaling pathways involved in numerous physiological processes (e.g., vasodilation, neurotransmission, inflammation, apoptosis, and tumor growth). Due to its gaseous form, NO has a short half‐life, and its physiology role is concentration dependent, often restricting its function to a target site. Providing NO from an external source is beneficial in promoting cellular functions and treatment of different pathological conditions. Hence, the multifaceted role of NO in physiology and pathology has garnered massive interest in developing strategies to deliver exogenous NO for the treatment of various regenerative and biomedical complexities. NO‐releasing platforms or donors capable of delivering NO in a controlled and sustained manner to target tissues or organs have advanced in the past few decades. This review article discusses in detail the generation of NO via the enzymatic functions of NO synthase as well as from NO donors and the multiple biological and pathological processes that NO modulates. The methods for incorporating of NO donors into diverse biomaterials including physical, chemical, or supramolecular techniques are summarized. Then, these NO‐releasing platforms are highlighted in terms of advancing treatment strategies for various medical problems.

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Section: No Production Signaling and Roles In Human Physiology And Di...mentioning

confidence: 99%

Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications

Andrabi,

Sharma,

Karan

et al. 2023

Advanced Science

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“…In recent years, one of the most exciting achievements in uncovering the role of NO in regulation of biofilm formation and dispersal has been the identification of NO signaling cascades, composed of at least one protein that senses NO and one protein that regulates gene expression and/or enzyme activity in response to NO [27,134]. To date, most of the characterized bacterial NO sensors belong to H-NOX (heme-nitric oxide or O 2 binding domain) proteins, which are homologous to the mammalian NO sensor, soluble guanylate cyclase [26,135,136]. Genes coding for NO-sensing H-NOX are frequently located next to those coding for its responding partners, such as cyclic di-GMP (c-di-GMP) synthases, or c-di-GMP phosphodiesterases, or histidine kinases of a two-component regulatory system [133,135].…”

Section: Regulation Of Bacterial Communitiesmentioning

confidence: 99%

Nitric Oxide, Nitric Oxide Formers and Their Physiological Impacts in Bacteria

Chen

Liu

Wang

et al. 2022

IJMS

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Nitric oxide (NO) is an active and critical nitrogen oxide in the microbe-driven nitrogen biogeochemical cycle, and is of great interest to medicine and the biological sciences. As a gas molecule prior to oxygen, NO respiration represents an early form of energy generation via various reactions in prokaryotes. Major enzymes for endogenous NO formation known to date include two types of nitrite reductases in denitrification, hydroxylamine oxidoreductase in ammonia oxidation, and NO synthases (NOSs). While the former two play critical roles in shaping electron transport pathways in bacteria, NOSs are intracellular enzymes catalyzing metabolism of certain amino acids and have been extensively studied in mammals. NO interacts with numerous cellular targets, most of which are redox-active proteins. Doing so, NO plays harmful and beneficial roles by affecting diverse biological processes within bacterial physiology. Here, we discuss recent advances in the field, including NO-forming enzymes, the molecular mechanisms by which these enzymes function, physiological roles of bacterial NOSs, and regulation of NO homeostasis in bacteria.

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“…The nitric oxide synthase (NOS) enzyme is responsible for the biosynthesis of nitric oxide (NO) in mammals . Nitric oxide (NO) is a ubiquitous intercellular signaling molecule that is important for neurotransmission, vasodilation, and innate immune response. − There are three mammalian NOS isoforms: neuronal, endothelial, and inducible NOS (nNOS, eNOS, and iNOS, respectively). Both nNOS and eNOS are constitutively expressed, while iNOS is transcriptionally controlled.…”

Section: Introductionmentioning

confidence: 99%

Mapping the Intersubunit Interdomain FMN-Heme Interactions in Neuronal Nitric Oxide Synthase by Targeted Quantitative Cross-Linking Mass Spectrometry

Jiang,

Wan,

Zhang

et al. 2024

Biochemistry

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Nitric oxide synthase (NOS) in mammals is a family of multidomain proteins in which interdomain electron transfer (IET) is controlled by domain–domain interactions. Calmodulin (CaM) binds to the canonical CaM-binding site in the linker region between the FMN and heme domains of NOS and allows tethered FMN domain motions, enabling an intersubunit FMN-heme IET in the output state for NO production. Our previous cross-linking mass spectrometric (XL MS) results demonstrated site-specific protein dynamics in the CaM-responsive regions of rat neuronal NOS (nNOS) reductase construct, a monomeric protein [Jiang et al., Biochemistry, 2023, 62, 2232–2237]. In this work, we have extended our combined approach of XL MS structural mapping and AlphaFold structural prediction to examine the homodimeric nNOS oxygenase/FMN (oxyFMN) construct, an established model of the NOS output state. We employed parallel reaction monitoring (PRM) based quantitative XL MS (qXL MS) to assess the CaM-induced changes in interdomain dynamics and interactions. Intersubunit cross-links were identified by mapping the cross-links onto top AlphaFold structural models, which was complemented by comparing their relative abundances in the cross-linked dimeric and monomeric bands. Furthermore, contrasting the CaM-free and CaM-bound nNOS samples shows that CaM enables the formation of the intersubunit FMN-heme docking complex and that CaM binding induces extensive, allosteric conformational changes across the NOS regions. Moreover, the observed cross-links sites specifically respond to changes in ionic strength. This indicates that interdomain salt bridges are responsible for stabilizing and orienting the output state for efficient FMN-heme IET. Taken together, our targeted qXL MS results have revealed that CaM and ionic strength modulate specific dynamic changes in the CaM/FMN/heme complexes, particularly in the context of intersubunit interdomain FMN-heme interactions.

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Revisiting Nitric Oxide Signaling: Where Was It, and Where Is It Going?

Cited by 13 publications

References 43 publications

Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications

Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications

Nitric Oxide, Nitric Oxide Formers and Their Physiological Impacts in Bacteria

Mapping the Intersubunit Interdomain FMN-Heme Interactions in Neuronal Nitric Oxide Synthase by Targeted Quantitative Cross-Linking Mass Spectrometry

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