Neuronal Nitric Oxide Synthase (nNOS) in Neutrophils: An Insight

Saini, Rashmi; Azam, Zaffar; Sapra, Leena; Srivastava, Rupesh K.

doi:10.1007/112_2021_61

Cited by 6 publications

(4 citation statements)

References 146 publications

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“…This interaction is mediated by the Cav1 scaffolding domain, which can bind to the caveolin-binding motif present in nNOS. This binding typically results in the inhibition of nNOS activity, similar to the mechanism by which Cav1 interacts with eNOS 49,65 . Dysregulation of the Cav1-nNOS interaction has been implicated in various diseases.…”

Section: Discussionmentioning

confidence: 87%

Genetic Manipulation of Caveolin-1 in the Mouse Model of Marfan Syndrome Associated Aortic Root Aneurysm: Effects on Endothelial and Smooth Muscle Function

Curry,

Gusek,

Potter

et al. 2024

Preprint

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Marfan Syndrome (MFS) is a systemic connective tissue disorder caused by mutations in the gene encoding for the large glycoprotein Fibrillin-1 (Fbn1), leading to wide-spectrum clinical manifestations, with the most life-threatening being aortic root aneurysm. MFS aortic aneurysm is known to be associated with reduced endothelial nitric oxide synthase (eNOS)-mediated nitric oxide (NO) production. Previous studies have shown that caveolin-1 (Cav1), a coat protein of caveolae structure on the plasma membrane, acts as a negative regulator of eNOS activity. This suggests that Cav1 may play a role in the development of aortic root aneurysm in MFS by modulating eNOS activity. In this study, we investigated the role of Cav1 in regulating aortic smooth muscle and endothelial function, aortic wall elasticity, and wall strength by generating MFS mice (FBN1+/Cys1041Gly) lacking Cav1 gene expression (MFS/Cav1KO). Our data show that ablation of the Cav1 gene results in a significant decrease in aortic smooth muscle contraction in response to the vasoconstricting agent phenylephrine seemingly due to a marked increase in NO production within the aortic wall. We also showed that acetylcholine-induced vasorelaxation was increased in MFS/Cav1KO mice potentially through the endothelial nitric oxide-dependent mechanism, further confirming inhibitory role of Cav1 on endothelial NO production. In addition, aortic wall elastin fiber structure and strength were markedly improved in male MFS/Cav1KO mice. This study demonstrates the regulatory role of Cav1 during the development of aortic root aneurysm in MFS mice through its effects on smooth muscle and endothelial functions in an NO-dependent manner.

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Section: Discussionmentioning

confidence: 87%

Genetic Manipulation of Caveolin-1 in the Mouse Model of Marfan Syndrome Associated Aortic Root Aneurysm: Effects on Endothelial and Smooth Muscle Function

Curry,

Gusek,

Potter

et al. 2024

Preprint

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“…In the central nervous system, nNOS is involved in regulating physiological functions such as memory, learning, neurogenesis and mediating long-term regulation of synaptic transmission. In addition, NO formed by nNOS in the central nervous system is involved in the central regulation of blood pressure [16]. In the periphery, many smooth muscle tissues are innervated by nitro-energic nerves, which are nerves that contain nNOS and produce and release NO.…”

Section: No/nos Pathway Overviewmentioning

confidence: 99%

Nitric Oxide Synthases in Rheumatoid Arthritis

et al. 2023

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe joint damage and disability. However, the specific mechanism of RA has not been thoroughly clarified over the past decade. Nitric oxide (NO), a kind of gas messenger molecule with many molecular targets, is demonstrated to have significant roles in histopathology and homeostasis. Three nitric oxide synthases (NOS) are related to producing NO and regulating the generation of NO. Based on the latest studies, NOS/NO signaling pathways play a key role in the pathogenesis of RA. Overproduction of NO can induce the generation and release of inflammatory cytokines and act as free radical gas to accumulate and trigger oxidative stress, which can involve in the pathogenesis of RA. Therefore, targeting NOS and its upstream and downstream signaling pathways may be an effective approach to managing RA. This review clearly summarizes the NOS/NO signaling pathway, the pathological changes of RA, the involvement of NOS/NO in RA pathogenesis and the conventional and novel drugs based on NOS/NO signaling pathways that are still in clinical trials and have good therapeutic potential in recent years, with an aim to provide a theoretical basis for further exploration of the role of NOS/NO in the pathogenesis, prevention and treatment of RA.

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“…NHERF1 belongs to the NHERF family of protein-protein interaction modules (PDZ)-scaffold proteins. The PDZ family of proteins is one of the largest in the human proteome including membrane-associated guanylate kinases (MAGUKs), involved in different molecular signal networks (4); nitric oxide synthase 1 (neuronal) (NOS1), engaged in neurotoxicity associated with neurodegenerative diseases (5); segment polarity protein dishevelled homolog DVL1-2-3 (DVL1-2-3), implicated in cell proliferation and molecular transducer for different human diseases (6). Scaffolding proteins play a critical role in coordinating cellular response by the assembly of multiple complexes that make faster and more effective the molecular signals.…”

Section: Structural and Functional Aspects Of Na(+)/h(+) Exchange Reg...mentioning

confidence: 99%

The Biological Relevance of NHERF1 Protein in Gynecological Tumors

et al. 2022

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Gynecological cancer management remains challenging and a better understanding of molecular mechanisms that lead to carcinogenesis and development of these diseases is needed to improve the therapeutic approaches. The Na+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein that contains modular protein-interaction domains able to interact with molecules with an impact on carcinogenesis and cancer progression. During recent years, its involvement in gynecological cancers has been explored, suggesting that NHERF1 could be a potential biomarker for the development of new targeted therapies suitable to the management of these tumors. This comprehensive review provides an update on the recent study on NHERF1 activity and its pathological role in cervical and ovarian cancer, as well as on its probable involvement in the therapeutic landscape of these cancer types.

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Neuronal Nitric Oxide Synthase (nNOS) in Neutrophils: An Insight

Cited by 6 publications

References 146 publications

Genetic Manipulation of Caveolin-1 in the Mouse Model of Marfan Syndrome Associated Aortic Root Aneurysm: Effects on Endothelial and Smooth Muscle Function

Genetic Manipulation of Caveolin-1 in the Mouse Model of Marfan Syndrome Associated Aortic Root Aneurysm: Effects on Endothelial and Smooth Muscle Function

Nitric Oxide Synthases in Rheumatoid Arthritis

The Biological Relevance of NHERF1 Protein in Gynecological Tumors

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