Emerging Roles of Hydrogen Sulfide in Inflammatory and Neoplastic Colonic Diseases

Guo, Fangfang; Yu, TaChung; Hong, Jie; Fang, Jing‐Yuan

doi:10.3389/fphys.2016.00156

Cited by 129 publications

(119 citation statements)

References 80 publications

(137 reference statements)

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“…H 2 S is an important mediator of many biological processes (angiogenesis, cytoprotection, metabolism, inflammation) and can be pro- or anti-inflammatory depending on its concentration and the particular circumstance3536. In light of these opposite effects, a recent study reported that paediatric CD patients undergoing EEN treatment and presenting with reduced colonic inflammation had increased levels of fecal H 2 S37.…”

Section: Discussionmentioning

confidence: 99%

Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease

et al. 2016

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Intestinal microbial dysbiosis is associated with Crohn's disease (CD). However, the mechanisms leading to the chronic mucosal inflammation that characterizes this disease remain unclear. In this report, we use systems-level approaches to study the interactions between the gut microbiota and host in new-onset paediatric patients to evaluate causality and mechanisms of disease. We report an altered host proteome in CD patients indicative of impaired mitochondrial functions. In particular, mitochondrial proteins implicated in H2S detoxification are downregulated, while the relative abundance of H2S microbial producers is increased. Network correlation analysis reveals that Atopobium parvulum controls the central hub of H2S producers. A. parvulum induces pancolitis in colitis-susceptible interleukin-10-deficient mice and this phenotype requires the presence of the intestinal microbiota. Administrating the H2S scavenger bismuth mitigates A. parvulum-induced colitis in vivo. This study reveals that host–microbiota interactions are disturbed in CD and thus provides mechanistic insights into CD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease

et al. 2016

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“…), found to be enriched in inflammatory bowel conditions as well as periodontal disease and metabolic syndrome[344,345], overlap significantly with those identified as pathogenic, nitratereducing Proteobacteria in the inflammatory gut and cystic fibrosis lung[323,337]. Indeed, there remains conflicting evidence regarding the precise role of H 2 S in the gut[344,347]. On one hand, it appears that lower concentrations of endogenously derived H 2 S exert beneficial cytoprotective, antioxidant and anti-inflammatory actions[344,348–351], while on the other, increased H 2 S formation by SRB can promote oxidant formation, impair colonic epithelial H 2 S detoxification and induce cytotoxicity and disruption of intestinal barrier integrity, thereby driving local and systemic inflammation[344,347,352,353].…”

Section: Dysbiosis Of the Microbiome In Pulmonary Hypertension And Vascmentioning

confidence: 99%

“…Indeed, there remains conflicting evidence regarding the precise role of H 2 S in the gut[344,347]. On one hand, it appears that lower concentrations of endogenously derived H 2 S exert beneficial cytoprotective, antioxidant and anti-inflammatory actions[344,348–351], while on the other, increased H 2 S formation by SRB can promote oxidant formation, impair colonic epithelial H 2 S detoxification and induce cytotoxicity and disruption of intestinal barrier integrity, thereby driving local and systemic inflammation[344,347,352,353]. Certainly, further understanding of the roles that H 2 S concentration, substrate, and location play in inflammation and nitrate metabolism remain to be more fully elucidated.…”

Section: Dysbiosis Of the Microbiome In Pulmonary Hypertension And Vascmentioning

confidence: 99%

Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health

Koch

Gladwin

Freeman

et al. 2017

Free Radical Biology and Medicine

145

127

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Recent insights into the bioactivation and signaling actions of inorganic, dietary nitrate and nitrite now suggest a critical role for the microbiome in the development of cardiac and pulmonary vascular diseases. Once thought to be the inert, end-products of endothelial-derived nitric oxide (NO) heme-oxidation, nitrate and nitrite are now considered major sources of exogenous NO that exhibit enhanced vasoactive signaling activity under conditions of hypoxia and stress. The bioavailability of nitrate and nitrite depend on the enzymatic reduction of nitrate to nitrite by a unique set of bacterial nitrate reductase enzymes possessed by specific bacterial populations in the mammalian mouth and gut. The pathogenesis of pulmonary hypertension (PH), obesity, hypertension and CVD are linked to defects in NO signaling, suggesting a role for commensal oral bacteria to shape the development of PH through the formation of nitrite, NO and other bioactive nitrogen oxides. Oral supplementation with inorganic nitrate or nitrate-containing foods exert pleiotropic, beneficial vascular effects in the setting of inflammation, endothelial dysfunction, ischemia-reperfusion injury and in pre-clinical models of PH, while traditional high-nitrate dietary patterns are associated with beneficial outcomes in hypertension, obesity and CVD. These observations highlight the potential of the microbiome in the development of novel nitrate- and nitrite-based therapeutics for PH, CVD and their risk factors.

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“…Hydrogen sulfide (H 2 S) is a gasotransmitter that regulates inflammatory and cell cycle processes(6). It is biosynthesized by three different enzymes, cystathionine γ-lyase (CSE), cystathionine ß-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST)(7).…”

Section: Introductionmentioning

confidence: 99%

HumanMETTL7BEncodes an Alkyl Thiol Methyltransferase that Methylates Hydrogen Sulfide

Maldonato

Totah

2020

Preprint

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Paragraph/Abstract: 27Methyltransferase-like protein 7B (METTL7B) is implicated in tumor growth and 28 progression while gene expression is upregulated in several different disease states such as 29 72 including hydrogen sulfide, captopril, 7α-thiospironolactone, D-and L-penicillamine, and the 73 active metabolites of prasugrel, and ziprasidone (1, 2,(23)(24)(25)(26)(27). However, despite numerous 74 attempts, researchers have not successfully identified the TMT gene or protein (28-31). 75Our preliminary approach to identify TMT expanded on earlier research which attempted 76 to purify TMT from rat liver microsomes using a number of chromatographic steps (28, 31). 77After significant increases in TMT specific activity, preliminary non-targeted proteomic 78 experiments were conducted to identify potential methyltransferase proteins in the TMT-active 79 fractions. The major candidate protein in active fractions was identified as rat METTL7B which 80 was also localized to the endoplasmic reticulum (Extended Data Table 1). Rat and human 81 METTL7B share 83% sequence homology, which suggests a conserved function. Subsequent 82 experiments modulating the expression of human METTL7B in two cell lines also altered 83 captopril methylation, a known TMT substrate. Once identified, we cloned, recombinantly84 expressed, and purified human full length METTL7B in E. coli and conducted small molecule 85 substrate screening with the purified protein. The activity screens confirmed that METTL7B 86 specifically catalyzes SAM-dependent methylation of aliphatic thiol compounds, including 87 hydrogen sulfide, in a time and protein concentration dependent manner. No methylation was 88 observed with classic probe substrates of other known small molecule S-, N-, and O-89 methyltransferases(32-36) or endogenous thiols such as cysteine or glutathione.90 91 92 93 109 B) Methylation of captopril activity significantly decreased in HepG2 cells treated with METTL7B siRNA compared 110 to control cells. C) HeLa cells treated with a METTL7B overexpression plasmid showed ~ 1,000-fold increase in 111 METT7B gene expression compared to control cells transfected with an empty expression vector. D) HeLa cells 112transfected with the METTL7B expression vector showed a 10-fold increase in captopril methylation activity 113 compared to negative control cells. E) FLAG-tagged METTL7B expression is only observed in cells treated with 114 the METTL7B overexpression plasmid compared to controls (Lanes 2 and 1 respectively). ß-actin was used as a 115 loading control. All data is presented as the mean ± standard deviation. Individual data points from two (A, C, and 116 D) or three (B) experiments are plotted. Significance was determined using unpaired two-tailed t test.

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Emerging Roles of Hydrogen Sulfide in Inflammatory and Neoplastic Colonic Diseases

Cited by 129 publications

References 80 publications

Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease

Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease

Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health

HumanMETTL7BEncodes an Alkyl Thiol Methyltransferase that Methylates Hydrogen Sulfide

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