Homocysteine (Hcy) is detrimental to bone health in a mouse model of diet-induced hyperhomocysteinemia (HHcy). However, little is known about Hcy-mediated osteoblast dysfunction via mitochondrial oxidative damage. Hydrogen sulfide (H2S) has potent antioxidant, anti-inflammatory, and antiapoptotic effects. In this study, we hypothesized that the H2S mediated recovery of osteoblast dysfunction by maintaining mitochondrial biogenesis in Hcy-treated osteoblast cultures in vitro. MC3T3-E1 osteoblastic cells were exposed to Hcy treatment in the presence or absence of an H2S donor (NaHS). Cell viability, osteogenic differentiation, reactive oxygen species (ROS) production were determined. Mitochondrial DNA copy number, adenosine triphosphate (ATP) production, and oxygen consumption were also measured. Our results demonstrated that administration of Hcy increases the intracellular Hcy level and decreases intracellular H2S level and expression of the cystathionine β-synthase/Cystathionine γ-lyase system, thereby inhibiting osteogenic differentiation. Pretreatment with NaHS attenuated Hcy-induced mitochondrial toxicity (production of total ROS and mito-ROS, ratio of mitochondrial fission (DRP-1)/fusion (Mfn-2)) and restored ATP production and mitochondrial DNA copy numbers as well as oxygen consumption in the osteoblast as compared with the control, indicating its protective effects against Hcy-induced mitochondrial toxicity. In addition, NaHS also decreased the release of cytochrome c from the mitochondria to the cytosol, which induces cell apoptosis. Finally, flow cytometry confirmed that NaHS can rescue cells from apoptosis induced by Hcy. Our studies strongly suggest that NaHS has beneficial effects on mitochondrial toxicity, and could be developed as a potential therapeutic agent against HHcy-induced mitochondrial dysfunction in cultured osteoblasts in vitro. 相似文献
Hyperhomocysteinemia (HHcy) is a critical independent risk factor for cardiovascular diseases. However, to date, no satisfactory
strategies to prevent HHcy exist. Since homocysteine (Hcy) and endogenous H2S are both metabolites of sulfur-containing amino acids, we aimed to investigate whether a metabolic product of Hcy and H2S, may antagonize in part the cardiovascular effects of Hcy. In the HHcy rat model injected subcutaneously with Hcy for 3 weeks,
H2S levels and the H2S-generating enzyme cystathionine γ lyase (CSE) activity in the myocardium were decreased. The intraperitoneal injection of
H2S gas saturation solution significantly reduced plasma total Hcy (tHcy) concentration and decreased lipid peroxidation formation
(i.e., lowered manodialdehyde and conjugated diene levels in myocardia and plasma). The activities of myocardial mitochondrial
respiratory enzymes succinate dehydrogenase, cytochrome oxidase, and manganese superoxide dismutase, related to reactive oxygen
species metabolism, were significantly dysfunctional in HHcy rats. The H2S administration restored the level of enzyme activities and accelerated the scavenging of H2O2 and superoxide anion generated by Hcy in isolated mitochondria. The H2S treatment also inhibited the expression of glucose-regulated protein 78, a marker of endoplasmic reticulum (ER) stress,
induced by Hcy in vivo and in vitro. Thus, HHcy impaired the myocardial CSE/H2S pathway, and the administration of H2S protected the myocardium from oxidative and ER stress induced by HHcy, which suggests that an endogenous metabolic balance
of sulfur-containing amino acids may be a novel strategy for treatment of HHcy. 相似文献
Gaseous molecules, such as hydrogen sulfide(H_2S)and nitric oxide(NO), are crucial players in cellular and(patho)physiological processes in biological systems. The biological functions of these gaseous molecules, which were first discovered and identified as gasotransmitters in animals, have received unprecedented attention from plant scientists in recent decades. Researchers have arrived at the consensus that H_2S is synthesized endogenously and serves as a signaling molecule throughout the plant life cycle.However, the mechanisms of H_2S action in redox biology is still largely unexplored. This review highlights what we currently know about the characteristics and biosynthesis of H_2S in plants. Additionally,we summarize the role of H_2S in plant resistance to abiotic stress. Moreover, we propose and discuss possible redox-dependent mechanisms by which H_2S regulates plant physiology. 相似文献
As a gasotransmitter, hydrogen sulfide (H2S) plays a crucial role in regulating the signaling pathway mediated by oxidative stress. The purpose of this study was to investigate the protective effects of H 2S on uranium‐induced rat hepatocyte cytotoxicity. Primary hepatocytes were isolated and cultured from Sprague Dawley rat liver tissues. After pretreating with sodium hydrosulfide (an H 2S donor) for 1 hour (or GKT‐136901 for 30 minutes), hepatocytes were treated by uranyl acetate for 24 hours. Cell viability, reactive oxygen species (ROS), malondialdehyde (MDA), NADPH oxidase 4 (Nox4), and p38 mitogen‐activated protein kinase (p38 MAPK) phosphorylation were respectively determined. The effects of direct inhibition of Nox4 expression by GKT‐136901 (a Nox4 inhibitor) on ROS and phospho‐p38 MAPK levels were examined in uranium‐treated hepatocytes. The results implicate that H 2S can afford protection of rat hepatocytes against uranium‐induced adverse effects through attenuating oxidative stress via prohibiting Nox4/ROS/p38 MAPK signaling. 相似文献
Hydrogen sulfide (H2S) is an important gaseous molecule in various plant developmental processes and plant stress responses. In this study, the transgenic Arabidopsis thaliana plants with modulated exp... 相似文献
The present study attempts to investigate the effect of H(2)S on lipopolysaccharide (LPS)-induced inflammation in both primary cultured microglia and immortalized murine BV-2 microglial cells. We found that exogenous application of sodium hydrosulfide (NaHS) (a H(2)S donor, 10-300 micro mol/L) attenuated LPS-stimulated nitric oxide (NO) in a concentration-dependent manner. Stimulating endogenous H(2)S production decreased LPS-stimulated NO production, whereas lowering endogenous H(2)S level increased basal NO production. Western blot analysis showed that both exogenous and endogenous H(2)S significantly attenuated the stimulatory effect of LPS on inducible nitric oxide synthase expression, which is mimicked by SB 203580, a specific p38 mitogen-activated protein kinase (MAPK) inhibitor. Exogenously applied NaHS significantly attenuated LPS-induced p38 MAPK phosphorylation in BV-2 microglial cells. Moreover, both NaHS (300 micro mol/L) and SB 203580 (1 micro mol/L) significantly attenuated LPS-induced tumor necrosis factor-alpha secretion, another inflammatory indicator. In addition, NaHS (10-300 micro mol/L) dose-dependently decreased LPS-stimulated NO production in primary cultured astrocytes, suggesting that the anti-neuroinflammatory effect of H(2)S is not specific to microglial cells alone. Taken together, H(2)S produced an anti-inflammatory effect in LPS-stimulated microglia and astrocytes, which may be due to inhibition of inducible nitric oxide synthase and p38 MAPK signaling pathways. These findings may have important implications in the treatment of neuroinflammation-related diseases. 相似文献
This study aimed to assess hydrogen sulfide (H2S) concentrations in the pool indoor air of hot springs and its link to some physicochemical properties of the springs in Ardabil province. Twenty-two hot springs from different regions were selected and monitored for H2S concentrations using a portable gas meter. Respective mean concentrations of H2S in hot springs indoor air were 9.11 ± 11. Ghotour Souei hot springs had the highest concentration of H2S with a mean concentration of 29.4 ± 7.7 and 25.2 ± 8.16 ppm at the source and general pool areas, respectively. Oxidation-reduction potential and pH of the water were the most important factor influencing H2S concentrations in the hot springs. H2S concentrations in indoor air of Ardabil hot springs were noticeably higher than OEL-TWA and OEL-STEL, and therefore may pose important risks for human health on both short-and long-term exposures. 相似文献
Hydrogen sulfide (H2S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2S is produced from substances by three enzymes: cystathionine β‐synthase (CBS), cystathionine γ‐lyase (CSE), and 3‐mercaptopyruvate sulfurtransferase (MST). In human tissues, these enzymes are involved in tissue‐specific biochemical pathways for H2S production. For example, CBS and cysteine aminotransferase/MST are present in the brain, but CSE is not. Thus, we examined the expression of H2S production‐related enzymes in peripheral nerves. Here, we found that CSE and MST/cysteine aminotransferase, but not CBS, were present in normal peripheral nerves. In addition, injured sciatic nerves in vivo up‐regulated CSE in Schwann cells during Wallerian degeneration (WD); however, CSE was not up‐regulated in peripheral axons. Using an ex vivo sciatic nerve explant culture, we found that the inhibition of H2S production broadly prevented the process of nerve degeneration, including myelin fragmentation, axonal degradation, Schwann cell dedifferentiation, and Schwann cell proliferation in vitro and in vivo. Thus, these results indicate that H2S signaling is essential for Schwann cell responses to peripheral nerve injury.
We have identified that hydrogen sulfide (H2S), a gaseous mediator, plays a crucial role in antioxidative, anti-inflammatory, and cytoprotective effects on uranium (U)-triggered rat nephrotoxicity. Pyroptosis is a special mode of inflammation and programmed cell death involved in the activation of inflammasome and Caspase-1 and the release of inflammatory cytokines. This study aims to confirm whether H2S can alleviate U-induced rat NRK-52E cell pyroptosis and to investigate the H2S underlying regulatory mechanism. Our results indicate that pretreatment with NaHS (an H2S donor) significantly inhibited U-increased reactive oxygen species level, NLRP3, apoptosis-related speck-like protein consisting of a caspase recruitment domain (ASC), and cleaved Caspase-1 proteins expression, gasdermin D messenger RNA (GSDMD mRNA) expression, interleukin (IL)−1β and IL-18 contents, lactate dehydrogenase leakage, and numbers of double-positive dying kidney cells. NaHS application evidently augmented phosphorylated PI3K, AKT, and mTOR expression as well as ratios of their respective phosphorylation to the corresponding total proteins which were downregulated by U treatment. But, LY294002 (a PI3K inhibitor) administration effectively abrogated the consequences of NaHS on the levels of p-PI3K, cleaved Caspase-1, ASC and NLRP3 proteins, GSDMD mRNA expression, and (IL)-1β and IL-18 contents. Simultaneously, LY294002 significantly reversed the effects of NaHS on U-induced pyroptosis rate and cytotoxicity. Taken together, these results indicate that H2S ameliorated U-triggered NRK-52E cells pyroptosis via upregulation of PI3K/AKT/mTOR pathway, suggesting a novel role for H2S in the management of nephrotoxicity caused by U exposure. 相似文献
H2S (hydrogen sulfide), regarded as the third gaseous transmitter, is implicated in ulcerative colitis and colorectal cancers. The present study investigates the effects of H2S on cell proliferation in human colon cancer HCT 116 cells and SW480 cells. We identified the two key enzymes, CBS and CSE, for H2S synthesis in HCT 116 cells. An exogenously administered H2S donor NaHS induced cell proliferation in a concentration‐dependent manner, with optimal proliferative concentration at 200 μmol/l. NaHS administration increased Akt and ERK phosphorylation. Blockade of Akt and ERK activation attenuated NaHS‐induced cell proliferation. Cell‐cycle analysis showed that NaHS treatment for 6 h decreased the proportion of cells in G0–G1 phase and increased the proportion of cells in S phase. Protein expressions of Cyclin D1 and PCNA (proliferating cell nuclear antigen) were not altered, but the cyclin‐dependent kinase inhibitor p21Waf1/Cip1 was inhibited significantly by NaHS treatment. NaHS significantly reduced NO metabolite levels. In conclusion, NaHS induced human colon cancer cell proliferation. This effect might be mediated by the increase of Akt and ERK phosphorylation and the decrease of p21Waf1/Cip1 expression and NO production. The results suggested a role for H2S in human colonic cancer development. 相似文献
Arterial thrombosis is a pivotal event in the development of cardiovascular diseases. Plasma and cellular proteins have the potential to influence thrombus morphology and function. This review summarizes the latest studies to use proteomic technologies to characterize the cellular and plasma components involved in arterial thrombosis, with a view to understanding the pathogenesis and treatment of acute cardiovascular diseases. Proteomic approaches have been extensively used to profile the proteome of endothelial cells, leukocytes, vascular smooth muscle cells, platelets and plasma in the search for risk factors for cardiovascular disease; however, further work is required to validate the direct contribution of these proteins to arterial thrombosis. 相似文献
The interplay between H2S and nitric oxide (NO) is thought to contribute to renal functions. The current study was designed to assess the role of NO in mediating the renoprotective effects of hydrogen sulfide in the 5/6 nephrectomy (5/6 Nx) animal model. Forty rats were randomly assigned to 5 experimental groups: (a) Sham; (b) 5/6 Nx; (c) 5/6Nx+sodium hydrosulfide-a donor of H 2S, (5/6Nx+sodium hydrosulfide [NaHS]); (d) 5/6Nx+NaHS+ L -NAME (a nonspecific nitric oxide synthase [NOS] inhibitor); (e) 5/6Nx+NaHS+aminoguanidine (a selective inhibitor of inducible NOS [iNOS]). Twelve weeks after 5/6 Nx, we assessed the expressions of iNOS and endothelial NOS (eNOS), oxidative/antioxidant status, renal fibrosis, urine N-acetyl-b-glucosaminidase (NAG) activity as the markers of kidney injury and various markers of apoptosis, inflammation, remodeling, and autophagy. NaHS treatment protected the animals against chronic kidney injury as depicted by improved oxidative/antioxidant status, reduced apoptosis, and autophagy and attenuated messenger RNA (mRNA) expression of genes associated with inflammation, remodeling, and NAG activity. Eight weeks Nω-nitro-l-arginine methyl ester ( L -NAME) administration reduced the protective effects of hydrogen sulfide. In contrast, aminoguanidine augmented the beneficial effects of hydrogen sulfide. Our finding revealed some fascinating interactions between NO and H 2S in the kidney. Moreover, the study suggests that NO, in an isoform-dependent manner, can exert renoprotective effects in 5/6 Nx model of CKD. 相似文献
The oscillation of intracellular calcium (Ca2+) concentration is a primary event in numerous biological processes in plants, including stress response. Hydrogen sulfide (H2S), an emerging gasotransmitter, was found to have positive effects in plants responding to chromium (Cr6+) stress through interacting with Ca2+ signaling. While Ca2+ resemblances H2S in mediating biotic and abiotic stresses, crosstalk between the two pathways remains unclear. In this study, Ca2+ signaling interacted with H2S to produce a complex physiological response, which enhanced the Cr6+ tolerance in foxtail millet (Setaria italica). Results indicate that Cr6+ stress activated endogenous H2S synthesis as well as Ca2+ signaling. Moreover, toxic symptoms caused by Cr6+ stress were strongly moderated by 50 μM H2S and 20 mM Ca2+. Conversely, treatments with H2S synthesis inhibitor and Ca2+ chelators prior to Cr6+-exposure aggravated these toxic symptoms. Interestingly, Ca2+ upregulated expression of two important factors in metal metabolism, MT3A and PCS, which participated in the biosynthesis of heavy metal chelators, in a H2S-dependent manner to cope with Cr6+ stress. These findings also suggest that the H2S dependent pathway is a component of the Ca2+ activating antioxidant system and H2S partially contributes Ca2+-activating antioxidant system. 相似文献
An elevated level of homocysteine (Hcy) leads to hyperhomocysteinemia (HHcy), which results in vascular dysfunction and pathological conditions identical to stroke symptoms. Hcy increases oxidative stress and leads to increase in blood–brain barrier permeability and leakage. Hydrogen sulfide (H2S) production during the metabolism of Hcy has a cerebroprotective effect, although its effectiveness in Hcy-induced neurodegeneration and neurovascular permeability is less explored. Therefore, the current study was designed to perceive the neuroprotective effect of exogenous H 2S against HHcy, a cause of neurodegeneration. To test this hypothesis, we used four groups of mice: control, Hcy, control + sodium hydrosulfide hydrate (NaHS), and Hcy + NaHS, and an HHcy mice model in Swiss albino mice by giving a dose of 1.8 g of dl -Hcy/L in drinking for 8–10 weeks. Mice that have 30 µmol/L Hcy were taken for the study, and a H 2S supplementation of 20 μmol/L was given for 8 weeks to all groups of mice. HHcy results in the rise of the levels of superoxide and nitrite, although a concomitant decrease in the level of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and arginase in oxidative stress and a concomitant decrease in the endogenous level of H 2S. Although H 2S supplementation ameliorated, the effect of HHcy and the levels of H 2S returned to the average level in HHcy animals supplemented with H 2S. Interestingly, H 2S supplementation ameliorated neurovascular remodeling and neurodegeneration. Thus, our study suggested that H 2S could be a beneficial therapeutic candidate for the treatment of Hcy-associated neurodegeneration, such as stroke and neurovascular disorders. 相似文献