NO-GC in cells 'off the beaten track'

Friebe, Andreas; Voussen, Barbara; Groneberg, Dieter

doi:10.1016/j.niox.2018.03.020

Cited by 16 publications

(17 citation statements)

References 103 publications

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“…In general, two alpha subunits (a 1 and a 2 ) and two beta subunits (b 1 and b 2 ) are recognized, but b 2 has not been identified at the protein level and does not generate a catalytically active sGC upon coexpression with the other subunits, thus indicating that the b 2 gene may be a pseudogene. 25,35,36 Most tissues possess the het-erodimers, a 1 b 1 (NO-GC1) and a 2 b 1 (NO-GC2), which have been shown to exhibit enzymatic activity and to be potentially expressed in almost all cell types except platelets and erythrocytes; however, the ratios of the isoforms in individual cell types are not known. 35 Under physiologically low NO concentrations, cNOS-generated NO reacts directly with the iron atom in the heme group of sGC to activate enzymatic conversion of guanosine 5¢-triphosphate (GTP) into the intracellular second messenger cGMP.…”

Section: Anmentioning

confidence: 99%

“…25,35,36 Most tissues possess the het-erodimers, a 1 b 1 (NO-GC1) and a 2 b 1 (NO-GC2), which have been shown to exhibit enzymatic activity and to be potentially expressed in almost all cell types except platelets and erythrocytes; however, the ratios of the isoforms in individual cell types are not known. 35 Under physiologically low NO concentrations, cNOS-generated NO reacts directly with the iron atom in the heme group of sGC to activate enzymatic conversion of guanosine 5¢-triphosphate (GTP) into the intracellular second messenger cGMP. cGMP exerts its effects primarily by cGMP-dependent protein kinase (protein kinase G or PKG).…”

Section: Anmentioning

confidence: 99%

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Nitric Oxide in Dental Pulp Tissue: From Molecular Understanding to Clinical Application in Regenerative Endodontic Procedures

2020

Tissue Engineering Part B: Reviews

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Nitric oxide (NO), which is synthesized by the enzyme NO synthase (NOS), is a versatile endogenous molecule with multiple biological effects on many tissues and organs. In dental pulp tissue, NO has been found to play multifaceted roles in regulating physiological activities, inflammation processes, and tissue repair events, such as cell proliferation, neuronal degeneration, angiogenesis, and odontoblastic differentiation. However, there is a deficiency of detailed discussion on the NO-mediated interactions between inflammation and reparative/ regenerative responses in wounded dental pulp tissue, which is a central determinant of ultimate clinical outcomes. Thus, the purpose of this review is to outline the current molecular understanding on the roles of Janusfaced molecule NO in dental pulp physiology, inflammation, and reparative activities. Based on this knowledge, advanced physicochemical techniques designed to manipulate the therapeutic potential of NOS and NO production in endodontic regeneration procedures are further discussed.

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Section: Anmentioning

confidence: 99%

Section: Anmentioning

confidence: 99%

Nitric Oxide in Dental Pulp Tissue: From Molecular Understanding to Clinical Application in Regenerative Endodontic Procedures

2020

Tissue Engineering Part B: Reviews

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“…The main receptor for NO is the NO-sensitive soluble guanylyl cyclase (NO-GC) [ 10 ], which is expressed in a variety of cell types [ 11 ] and signals through cGMP on to cGMP-dependent protein kinase (PKG), phosphodiesterases or, possibly, on to cGMP-regulated channels [ 12 ]. The receptor for NO is not G-protein coupled, but cytoplasmic and composed of α (α1, α2) and β (β1) subunits of sGC, α1β1 being the most common.…”

Section: Nitric Oxidementioning

confidence: 99%

Nitric Oxide: From Gastric Motility to Gastric Dysmotility

Idrizaj

Traini

Vannucchi

et al. 2021

IJMS

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It is known that nitric oxide (NO) plays a key physiological role in the control of gastrointestinal (GI) motor phenomena. In this respect, NO is considered as the main non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmitter responsible for smooth muscle relaxation. Moreover, many substances (including hormones) have been reported to modulate NO production leading to changes in motor responses, further underlying the importance of this molecule in the control of GI motility. An impaired NO production/release has indeed been reported to be implicated in some GI dysmotility. In this article we wanted to focus on the influence of NO on gastric motility by summarizing knowledge regarding its role in both physiological and pathological conditions. The main role of NO on regulating gastric smooth muscle motor responses, with particular reference to NO synthases expression and signaling pathways, is discussed. A deeper knowledge of nitrergic mechanisms is important for a better understanding of their involvement in gastric pathophysiological conditions of hypo- or hyper-motility states and for future therapeutic approaches. A possible role of substances which, by interfering with NO production, could prove useful in managing such motor disorders has been advanced.

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“…Many questions regarding sGC have been investigated over the last 30 years, including (1) identification and cloning of the genes for the subunits, (2) the mechanism of NO activation, (3) identification of non-NO compounds that activate the enzyme, (4) structure of the enzyme, and (5) physiological and pathophysiological functions in different species (for review see e.g. Buys et al 2018;Childers and Garcin 2018;Friebe et al 2018;Horst and Marletta 2018;Koesling et al 2016). But still these and many other unsolved issues motivate researchers to produce novel and fascinating data, part of which were presented in Mainz.…”

Section: New Developments In Cgmp Signaling Sgc Structure and Functionmentioning

confidence: 99%

“…Pericytes are key cells for fibrosis and pericytic sGC expression has been shown in all organs so far investigated (Friebe et al 2018). Fibrotic responses in lung, liver, and skin are likely to involve sGC and the formation of myofibroblasts.…”

Section: The Role Of Cgmp In Fibrotic Remodeling and Fibrotic Diseasesmentioning

confidence: 99%

cGMP: a unique 2nd messenger molecule – recent developments in cGMP research and development

Friebe

Sandner

Schmidtko

2019

Naunyn-Schmiedeberg's Arch Pharmacol

Self Cite

101

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Cyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. cGMP targets a variety of downstream effector molecules and, thus, elicits a very broad variety of cellular effects. Its production is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC); both enzymes exist in different isoforms. cGMP-induced effects are regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). Depending on the distribution of sGC and pGC and the formation of ligands, this pathway regulates not only the cardiovascular system but also the kidney, lung, liver, and brain function; in addition, the cGMP pathway is involved in the pathogenesis of fibrosis, inflammation, or neurodegeneration and may also play a role in infectious diseases such as malaria. Moreover, new pharmacological approaches are being developed which target sGC-and pGC-dependent pathways for the treatment of various diseases. Therefore, it is of key interest to understand this pathway from scratch, beginning with the molecular basis of cGMP generation, the structure and function of both guanylyl cyclases and cGMP downstream targets; research efforts also focus on the subsequent signaling cascades, their potential crosstalk, and also the translational and, ultimately, the clinical implications of cGMP modulation. This review tries to summarize the contributions to the "9th International cGMP Conference on cGMP Generators, Effectors and Therapeutic Implications" held in Mainz in 2019. Presented data will be discussed and extended also in light of recent landmark findings and ongoing activities in the field of preclinical and clinical cGMP research.

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NO-GC in cells 'off the beaten track'

Cited by 16 publications

References 103 publications

Nitric Oxide in Dental Pulp Tissue: From Molecular Understanding to Clinical Application in Regenerative Endodontic Procedures

Nitric Oxide in Dental Pulp Tissue: From Molecular Understanding to Clinical Application in Regenerative Endodontic Procedures

Nitric Oxide: From Gastric Motility to Gastric Dysmotility

cGMP: a unique 2nd messenger molecule – recent developments in cGMP research and development

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