The role of hydrogen sulphide signalling in macrophage activation

Sun, Fei; Luo, Jun; Yue, Tian-Tian; Wang, Fa-Xi; Yang, Chunliang; Zhang, Jing; Wang, Xinqiang; Wang, Cong-Yi

doi:10.1111/imm.13253

Cited by 27 publications

(25 citation statements)

References 81 publications

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“…In mammals, three enzymes are responsible for H 2 S production: cystathionine γ-lyase (CSE), cystathionineβ-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST). CSE and CBS catalyze the de-sulfhydration of l -cysteine to generate H 2 S, while 3-MST generates H 2 S by modulating the activity of the cysteine aminotransferase (CAT) enzyme [ [12] , [13] , [14] , [15] ]. All three enzymes belong to the transsulfuration pathway (TSP), a complex multi-step pathway, which not only is deputed to the generation of H 2 S from l -cysteine, but also leads to other key metabolites including glutathione (GSH) and l -taurine.…”

Section: Introductionmentioning

confidence: 99%

“…However, it is important to consider that excessive reductive stress could be detrimental as is oxidative stress in tissues, skeletal muscle and heart included [ 21 ]. The anti-inflammatory and anti-oxidant action of H 2 S has been demonstrated in many types of human disorders [ 15 , 22 , 23 ] but its involvement in SKM diseases remains largely unknown. Recently, the role of the H 2 S signalling in skeletal muscle has been investigated showing that H 2 S biosynthesis is increased in Malignant Hyperthermia, a human syndrome characterized by an anomalous SKM hypercontractility following exposure to volatile anaesthetics, and this consequence contributes to the pathological hypercontractility observed [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Duchenne's muscular dystrophy involves a defective transsulfuration pathway activity

et al. 2021

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Duchenne muscular dystrophy (DMD) is the most frequent X chromosome-linked disease caused by mutations in the gene encoding for dystrophin, leading to progressive and unstoppable degeneration of skeletal muscle tissues. Despite recent advances in the understanding of the molecular processes involved in the pathogenesis of DMD, there is still no cure. In this study, we aim at investigating the potential involvement of the transsulfuration pathway (TSP), and its by-end product namely hydrogen sulfide (H 2 S), in primary human myoblasts isolated from DMD donors and skeletal muscles of dystrophic ( mdx ) mice. In myoblasts of DMD donors, we demonstrate that the expression of key genes regulating the H 2 S production and TSP activity, including cystathionine γ lyase (CSE), cystathionine beta-synthase (CBS), 3 mercaptopyruvate sulfurtransferase (3-MST), cysteine dioxygenase (CDO), cysteine sulfonic acid decarboxylase (CSAD), glutathione synthase (GS) and γ -glutamylcysteine synthetase (γ-GCS) is reduced. Starting from these findings, using Nuclear Magnetic Resonance (NMR) and quantitative Polymerase Chain Reaction (qPCR) we show that the levels of TSP-related metabolites such as methionine, glycine, glutathione, glutamate and taurine, as well as the expression levels of the aforementioned TSP related genes, are significantly reduced in skeletal muscles of mdx mice compared to healthy controls, at both an early (7 weeks) and overt (17 weeks) stage of the disease. Importantly, the treatment with sodium hydrosulfide (NaHS), a commonly used H 2 S donor, fully recovers the impaired locomotor activity in both 7 and 17 old mdx mice. This is an effect attributable to the reduced expression of pro-inflammatory markers and restoration of autophagy in skeletal muscle tissues. In conclusion, our study uncovers a defective TSP pathway activity in DMD and highlights the role of H 2 S-donors for novel and safe adjuvant therapy to treat symptoms of DMD.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Duchenne's muscular dystrophy involves a defective transsulfuration pathway activity

et al. 2021

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“…H 2 S is a gasotransmitter that exhibit anti-inflammatory properties, in part through the regulation of macrophage inflammatory status (Sun et al, 2020; Wallace et al, 2012). H 2 S donors have been widely used in vivo using animal models to treat various pathological conditions (Fagone et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Alteration of H 2 S levels have been associated with several diseases in human or animal models, including sepsis, diabetes or rheumatoid arthritis (Fagone et al, 2018). H 2 S has emerged as a promoter of the resolution of inflammation through the regulation of macrophage inflammatory state (Sun et al, 2020; Wallace et al, 2012). Interestingly, H 2 S-releasing molecules, like NaHS, have been shown to reduce skeletal muscle atrophy in a mouse model of diabetes (Lu et al, 2020) and to decrease muscle fibrosis after contusion-induced injury (Zhao et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Myofiber / pro-inflammatory macrophage interplay controls muscle damage in mdx mice

Saclier

Larbi

Moulin

et al. 2020

Preprint

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SummaryDuchenne Muscular Dystrophy is a genetic muscle disease characterized by chronic inflammation and fibrosis, which is mediated by a pro-fibrotic macrophage population expressing pro-inflammatory markers. The aim of this study was to characterize cellular events leading to the alteration of macrophage properties, and to modulate macrophage inflammatory status using the gaseous mediator H2S. We first analyzed the relationship between myofibers and macrophages in the mdx mouse model of Duchenne Muscular Dystrophy using coculture experiments. We showed that normal myofibers derived from mdx mice strongly skewed the polarization of resting macrophages towards a pro-inflammatory phenotype. Treatment of mdx mice with NaHS, an H2S donor, reduced the number of pro-inflammatory macrophages in skeletal muscle, which was associated with a decrease in the number of nuclei per fiber, a reduction of myofiber branching and a reduced fibrosis. These results identify an interplay between myofibers and macrophages where dystrophic myofibers contribute to the maintenance of a highly inflammatory environment that skews the macrophage status, which in turn favors myofiber damage, myofiber branching and fibrosis establishment. They also identify H2S donors as a potential therapeutic strategy to improve dystrophic muscle phenotype by modulating macrophage inflammatory status.

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“…Sulfide triggers induction of endogenous mammalian antioxidant defenses protecting cells from infection-associated oxidative stress [ 36 , 37 ]. It also inhibits the inflammatory response by suppressing the endotoxin-induced tumor necrosis factor a (TNF

) produced by macrophages [ 31 , 37 , 38 , 39 ].…”

Section: H 2 S In Host-pathogen Interactionsmentioning

confidence: 99%

Hydrogen Sulfide and Carbon Monoxide Tolerance in Bacteria

2021

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Hydrogen sulfide and carbon monoxide share the ability to be beneficial or harmful molecules depending on the concentrations to which organisms are exposed. Interestingly, humans and some bacteria produce small amounts of these compounds. Since several publications have summarized the recent knowledge of its effects in humans, here we have chosen to focus on the role of H2S and CO on microbial physiology. We briefly review the current knowledge on how bacteria produce and use H2S and CO. We address their potential antimicrobial properties when used at higher concentrations, and describe how microbial systems detect and survive toxic levels of H2S and CO. Finally, we highlight their antimicrobial properties against human pathogens when endogenously produced by the host and when released by external chemical donors.

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The role of hydrogen sulphide signalling in macrophage activation

Abstract: Cellular H2S content is linked to macrophage functional status. H2S signalling regulates activation of macrophage. Targeting on H2S signalling modules represents a promising approach in treating macrophage‐related disorders.

Cited by 27 publications

References 81 publications

Duchenne's muscular dystrophy involves a defective transsulfuration pathway activity

Duchenne's muscular dystrophy involves a defective transsulfuration pathway activity

Myofiber / pro-inflammatory macrophage interplay controls muscle damage in mdx mice

Hydrogen Sulfide and Carbon Monoxide Tolerance in Bacteria

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