Nitric oxide and hydrogen sulfide: Sibling rivalry in the family of epigenetic regulators

Kuschman, Hannah Petraitis; Palczewski, Marianne B.; Thomas, Douglas D.

doi:10.1016/j.freeradbiomed.2021.01.010

Cited by 25 publications

(13 citation statements)

References 126 publications

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“…An interesting aspect of this mechanism is that picolinic acid is a powerful intracellular metal chelator, which can lead to modification of PHD which regulates HIF1α and IKKα as well as epigenetic events [116]. In some cases, this can lead to increased NOS2 expression, suggesting an alternative tuning mechanism of this system [117]. Thus, the collaboration between arginine and tryptophan metabolism is antagonistic with respect polyamine versus NO synthesis.…”

Section: Tryptophanmentioning

confidence: 99%

Nitric Oxide Modulates Metabolic Processes in the Tumor Immune Microenvironment

McGinity

Palmieri

Somasundaram

et al. 2021

IJMS

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The metabolic requirements and functions of cancer and normal tissues are vastly different. Due to the rapid growth of cancer cells in the tumor microenvironment, distorted vasculature is commonly observed, which creates harsh environments that require rigorous and constantly evolving cellular adaption. A common hallmark of aggressive and therapeutically resistant tumors is hypoxia and hypoxia-induced stress markers. However, recent studies have identified alterations in a wide spectrum of metabolic pathways that dictate tumor behavior and response to therapy. Accordingly, it is becoming clear that metabolic processes are not uniform throughout the tumor microenvironment. Metabolic processes differ and are cell type specific where various factors promote metabolic heterogeneity within the tumor microenvironment. Furthermore, within the tumor, these metabolically distinct cell types can organize to form cellular neighborhoods that serve to establish a pro-tumor milieu in which distant and spatially distinct cellular neighborhoods can communicate via signaling metabolites from stroma, immune and tumor cells. In this review, we will discuss how biochemical interactions of various metabolic pathways influence cancer and immune microenvironments, as well as associated mechanisms that lead to good or poor clinical outcomes.

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Section: Tryptophanmentioning

confidence: 99%

Nitric Oxide Modulates Metabolic Processes in the Tumor Immune Microenvironment

McGinity

Palmieri

Somasundaram

et al. 2021

IJMS

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“…Specifically, NO plays a significant role in the regulation of nerve development and neurotransmission, insulin secretion, airway tone, immune response reaction, wound healing and intestinal peristalsis [ 36 , 50 ]. In addition, it is becoming apparent that NO also functions as an endogenous regulator in epigenetics, including DNA methylation, DNA demethylation and histone post-translational modifications [ 51 ]. Moreover, NO has been shown to counteract oxidative stress, inhibit cell death and facilitate pathogen scavenging [ 44 ].…”

Section: Gaseous Mediatorsmentioning

confidence: 99%

“…H 2 S also affects the functions of many other systems, such as the reproductive system, digestive system and endocrine system [ 77 ]. Notably, similar to NO, H 2 S is discovered to be an important endogenous epigenetic modulator [ 51 ]. Aberrant H 2 S metabolism occurs in many pathological states, such as sepsis, inflammation, coronavirus disease 2019, hypertension, atherosclerosis, obstructive respiratory disease, lung injury, macrophage activation, retinal diseases and neurodegenerative disease [ 77 , 81 , 86 , 87 , 88 , 89 ].…”

Section: Gaseous Mediatorsmentioning

confidence: 99%

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Zhu

Chambers

Zeng

et al. 2022

IJMS

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Sepsis, a potentially lethal condition resulting from failure to control the initial infection, is associated with a dysregulated host defense response to pathogens and their toxins. Sepsis remains a leading cause of morbidity, mortality and disability worldwide. The pathophysiology of sepsis is very complicated and is not yet fully understood. Worse still, the development of effective therapeutic agents is still an unmet need and a great challenge. Gases, including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), are small-molecule biological mediators that are endogenously produced, mainly by enzyme-catalyzed reactions. Accumulating evidence suggests that these gaseous mediators are widely involved in the pathophysiology of sepsis. Many sepsis-associated alterations, such as the elimination of invasive pathogens, the resolution of disorganized inflammation and the preservation of the function of multiple organs and systems, are shaped by them. Increasing attention has been paid to developing therapeutic approaches targeting these molecules for sepsis/septic shock, taking advantage of the multiple actions played by NO, CO and H2S. Several preliminary studies have identified promising therapeutic strategies for gaseous-mediator-based treatments for sepsis. In this review article, we summarize the state-of-the-art knowledge on the pathophysiology of sepsis; the metabolism and physiological function of NO, CO and H2S; the crosstalk among these gaseous mediators; and their crucial effects on the development and progression of sepsis. In addition, we also briefly discuss the prospect of developing therapeutic interventions targeting these gaseous mediators for sepsis.

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“…In this line, the oxygenation of the tissues is a main factor when the rather controversial results of gasotransmitter reactions are discussed. For example, the most important physiological mechanism linked to NO metabolism requires proper O 2 concentrations; under normal or higher O 2 tension, the half-life of NO is shorter, while in hypoxic environments NO will be eliminated after a significantly longer time with a number of prolonged effects (Kuschman et al, 2021). Likewise, a combination of low O 2 tension with mitochondria-derived ROS and higher NO flows leads to peroxynitrite formation (Thomas et al, 2008) with nitroxidative stress and post-translational protein modification (Campolo et al, 2020).…”

Section: Hypoxia and Inhaled Bioactive Gasesmentioning

confidence: 99%

Bioactivity of Inhaled Methane and Interactions With Other Biological Gases

Juhász

Tallósy

Nászai

et al. 2022

Front. Cell Dev. Biol.

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A number of studies have demonstrated explicit bioactivity for exogenous methane (CH4), even though it is conventionally considered as physiologically inert. Other reports cited in this review have demonstrated that inhaled, normoxic air-CH4 mixtures can modulate the in vivo pathways involved in oxidative and nitrosative stress responses and key events of mitochondrial respiration and apoptosis. The overview is divided into two parts, the first being devoted to a brief review of the effects of biologically important gases in the context of hypoxia, while the second part deals with CH4 bioactivity. Finally, the consequence of exogenous, normoxic CH4 administration is discussed under experimental hypoxia- or ischaemia-linked conditions and in interactions between CH4 and other biological gases, with a special emphasis on its versatile effects demonstrated in pulmonary pathologies.

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Nitric oxide and hydrogen sulfide: Sibling rivalry in the family of epigenetic regulators

Cited by 25 publications

References 126 publications

Nitric Oxide Modulates Metabolic Processes in the Tumor Immune Microenvironment

Nitric Oxide Modulates Metabolic Processes in the Tumor Immune Microenvironment

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Bioactivity of Inhaled Methane and Interactions With Other Biological Gases

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