共查询到20条相似文献,搜索用时 15 毫秒
1.
Hydrogen sulfide (H 2S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the central nervous system. The present study was undertaken to study the effects of exogenous H 2S on traumatic brain injury (TBI) and the underlying mechanisms. The effects of exogenous H 2S on TBI were examined by using measurement of brain edema, behavior assessment, propidium iodide (PI) staining, and Western blotting, respectively. Compared to TBI groups, H 2S pretreatment had reduced brain edema, improved motor performance and ameliorated performance in Morris water maze test after TBI. Immunoblotting results showed that H 2S pretreatment reversed TBI-induced cleavage of caspase-3 and decline of Bcl-2, suppressed LC3-II, Beclin-1 and Vps34 activation and maintained p62 level in injured cortex and hippocampus post TBI. The results suggest a protective effect and therapeutic potential of H 2S in the treatment of brain injury and the protective effect against TBI may be associated with regulating apoptosis and autophagy. 相似文献
2.
Hydrogen sulfide (H 2S) is a gaseous messenger and serves as an important neuromodulator in the central nervous system. The current study was undertaken
to investigate whether H 2S attenuates the neuronal injury induced by vascular dementia (VD). Rats were subjected to bilateral common carotid artery
and vertebral artery occlusion for 5 min three times in an interval of 5 min to induce VD. An H 2S donor, sodium hydrosulfide (NaHS) or an inhibitor of cystathionine-β-synthase, hydroxylamine (HA) was administered intraperitoneally.
The number of neurons in the hippocampus was determined by hematoxylin and eosin staining, and the performance of learning
and memory was tested by the Morris water maze. H 2S content in plasma was evaluated. Apoptosis in the hippocampus was assessed by flow cytometry. In addition, Bcl-2 and Bax
expression was analyzed by immunohistochemical staining. The neuronal injury occurred gradually with a decreased number of
neurons and increased apoptosis ratio in the hippocampus over 720 h after VD. The H 2S level was also gradually decreased in plasma over 720 h after VD, which negatively correlated with the apoptosis ratio in
the hippocampus after VD. In addition, NaHS treatment significantly attenuated neuronal injury and improved neural functional
performance, whereas HA exaggerated the neuronal injury and exacerbated learning and memory at 720 h after VD. Furthermore,
NaHS treatment markedly improved the ratio of Bcl-2 over Bax with increased Bcl-2 expression and decreased Bax expression.
In contrast, HA reduced the ratio of Bcl-2 over Bax. It is suggested that H 2S attenuates VD injury via inhibiting apoptosis and may have potential therapeutic value for VD. 相似文献
3.
Hydrogen sulfide (H 2S) produced by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in the transsulfuration pathway of homocysteine plays a number of pathophysiological roles. Hyperhomocysteinemia is involved in kidney fibrosis. However, the role of H 2S in kidney fibrosis remains to be defined. Here, we investigated the role of H 2S and its acting mechanism in unilateral ureteral obstruction (UO)-induced kidney fibrosis in mice. UO decreased expressions of CBS and CSE in the kidney with decrease of H 2S concentration. Treatment with sodium hydrogen sulfide (NaHS, a H 2S producer) during UO reduced UO-induced oxidative stress with preservations of catalase, copper-zinc superoxide dismutase (CuZnSOD), and manganese superoxide dismutase (MnSOD) expression, and glutathione level. In addition, NaHS mitigated decreases of CBS and CSE expressions, and H 2S concentration in the kidney. NaHS treatment attenuated UO-induced increases in levels of TGF-β1, activated Smad3, and activated NF-κB. This study provided the first evidence of involvement of the transsulfuration pathway and H 2S in UO-induced kidney fibrosis, suggesting that H 2S and its transsulfuration pathway may be a potential target for development of therapeutics for fibrosis-related diseases. 相似文献
4.
Hyperglycemia (HG) reduces AMPK activation leading to impaired autophagy and matrix accumulation. Hydrogen sulfide (H 2S) treatment improves HG-induced renovascular remodeling however, its mechanism remains unclear. Activation of LKB1 by the formation of heterotrimeric complex with STRAD and MO25 is known to activate AMPK. We hypothesized that in HG; H 2S induces autophagy and modulates matrix synthesis through AMPK-dependent LKB1/STRAD/MO25 complex formation. To address this hypothesis, mouse glomerular endothelial cells were treated with normal and high glucose in the absence or presence of sodium hydrogen sulfide (NaHS), an H 2S donor. HG decreased the expression of H 2S regulating enzymes CBS and CSE, and autophagy markers Atg5, Atg7, Atg3 and LC3B/A ratio. HG increased galectin-3 and periostin, markers of matrix accumulation. Treatment with NaHS to HG cells increased LKB1/STRAD/MO25 formation and AMPK phosphorylation. Silencing the encoded genes confirmed complex formation under normoglycemia. H 2S-mediated AMPK activation in HG was associated with upregulation of autophagy and diminished matrix accumulation. We conclude that H 2S mitigates adverse remodeling in HG by induction of autophagy and regulation of matrix metabolism through LKB1/STRAD/MO25 dependent pathway. 相似文献
5.
Many studies have demonstrated the cytoprotective effects of hydrogen sulfide (H 2S) in vitro and/or in vivo ischemic injury. The aim of the current study was to investigate whether exogenous H 2S attenuates the neuronal injury induced by brain ischemia. As an H 2S donor, sodium hydrosulfide (NaHS) was administered intraperitoneally (5.6 mg/kg/day, i.p.). The effects of exogenous H 2S on neurons of ischemic hippocampus were examined by using measurement of behavior, electrophysiology, morphology and immunohistochemical
staining, respectively. Our results showed that exogenous H 2S significantly improved spatial learning and memory deficits induced by brain ischemia ( P < 0.01). Exogenous H 2S enhanced synaptic plasticity in the hippocampus of brain-ischemic rats, inhibited the edema around pyramidal neurons and
the nuclear shrink induced by ischemia, and promoted the expression of growth-associated protein-43 (GAP-43) in the CA1 region
of hippocampus post ischemia. The results suggest a protective effect and therapeutic potential of H 2S in the treatment of brain ischemia. 相似文献
6.
Hydrogen sulfide (H 2S) plays an important role in human physiology, exerting vasodilatory, neuromodulatory and anti-inflammatory effects. H 2S has been implicated in the mechanism of gastrointestinal integrity but whether this gaseous mediator can affect hemorrhagic lesions induced by stress has been little elucidated. We studied the effect of the H 2S precursor L-cysteine, H 2S-donor NaHS, the H 2S synthesizing enzyme (CSE) activity inhibitor- D,L-propargylglycine (PAG) and the gastric H 2S production by CSE/CBS/3-MST activity in water immersion and restraint stress (WRS) ulcerogenesis and the accompanying changes in gastric blood flow (GBF). The role of endogenous prostaglandins (PGs) and sensory afferent nerves releasing calcitonin gene-related peptide (CGRP) in the mechanism of gastroprotection induced by H 2S was examined in capsaicin-denervated rats and those pretreated with capsazepine to inhibit activity of vanilloid receptors (VR-1). Rats were pretreated with vehicle, NaHS, the donor of H 2S and or L-cysteine, the H 2S precursor, with or without the concurrent treatment with 1) nonselective (indomethacin) and selective cyclooxygenase (COX)-1 (SC-560) or COX-2 (rofecoxib) inhibitors. The expression of mRNA and protein for COX-1 and COX-2 were analyzed in gastric mucosa pretreated with NaHS with or without PAG. Both NaHS and L-cysteine dose-dependently attenuated severity of WRS-induced gastric lesions and significantly increased GBF. These effects were significantly reduced by pretreatment with PAG and capsaicin denervation. NaHS increased gastric H 2S production via CSE/CBS but not 3-MST activity. Inhibition of COX-1 and COX-2 activity significantly diminished NaHS- and L-cysteine-induced protection and hyperemia. NaHS increased expression of COX-1, COX-2 mRNAs and proteins and raised CGRP mRNA expression. These effects of NaHS on COX-1 and COX-2 protein contents were reversed by PAG and capsaicin denervation. We conclude that H 2S exerts gastroprotection against WRS-induced gastric lesions by the mechanism involving enhancement in gastric microcirculation mediated by endogenous PGs, sensory afferent nerves releasing CGRP and the activation of VR-1 receptors. 相似文献
7.
Hydrogen sulfide (H 2S), a gasotransmitter endogenously found in the central nervous system, has recently been suggested to act as a signalling molecule in the brain having beneficial effects on cardiovascular function. This study was thus undertaken to investigate the effect of NaHS (an H 2S donor) in the subfornical organ (SFO), a central nervous system site important to blood pressure regulation. We used male Sprague-Dawley rats for both in vivo and in vitro experiments. We first used RT-PCR to confirm our previous microarray analyses showing that mRNAs for the enzymes required to produce H 2S are expressed in the SFO. We then used microinjection techniques to investigate the physiological effects of NaHS in SFO, and found that NaHS microinjection (5 nmol) significantly increased blood pressure (mean AUC = 853.5±105.7 mmHg*s, n = 5). Further, we used patch-clamp electrophysiology and found that 97.8% (88 of 90) of neurons depolarized in response to NaHS. This response was found to be concentration dependent with an EC 50 of 35.6 µM. Coupled with the depolarized membrane potential, we observed an overall increase in neuronal excitability using an analysis of rheobase and action potential firing patterns. This study has provided the first evidence of NaHS and thus H 2S actions and their cellular correlates in SFO, implicating this brain area as a site where H 2S may act to control blood pressure. 相似文献
8.
Hydrogen sulfide (H 2S), a gasotransmitter, exerts both neurotoxicity and neuroprotection, and targets multiple molecules including NMDA receptors, T-type calcium channels and NO synthase (NOS) that might affect neuronal viability. Here, we determined and characterized effects of NaHS, an H 2S donor, on cell viability in the primary cultures of mouse fetal cortical neurons. NaHS caused neuronal death, as assessed by LDH release and trypan blue staining, but did not significantly reduce the glutamate toxicity. The neurotoxicity of NaHS was resistant to inhibitors of NMDA receptors, T-type calcium channels and NOS, and was blocked by inhibitors of MEK, but not JNK, p38 MAP kinase, PKC and Src. NaHS caused prompt phosphorylation of ERK and upregulation of Bad, followed by translocation of Bax to mitochondria and release of mitochondrial cytochrome c, leading to the nuclear condensation/fragmentation. These effects of NaHS were suppressed by the MEK inhibitor. Our data suggest that the NMDA receptor-independent neurotoxicity of H 2S involves activation of the MEK/ERK pathway and some apoptotic mechanisms. 相似文献
9.
The effect of hydrogen sulfide (H 2S) on differentiation of 3T3L1-derived adipocytes was examined. Endogenous H 2S was increased after 3T3L1 differentiation. The expression of the H 2S-synthesising enzymes, cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), was increased in a time-dependent manner during 3T3L1 differentiation. Expression of genes associated with adipogenesis related genes including fatty acid binding protein 4 (FABP4/aP2), a key regulator of this process, was increased by GYY4137 (a slow-releasing H 2S donor compound) and sodium hydrosulfide (NaHS, a classical H 2S donor) but not by ZYJ1122 or time-expired NaHS. Furthermore expression of these genes were reduced by aminooxyacetic acid (AOAA, CBS inhibitor), DL-propargylglycine (PAG, CSE inhibitor) as well as by CSE small interference RNA (siCSE) and siCBS. The size and number of lipid droplets in mature adipocytes was significantly increased by both GYY4137 and NaHS, which also impaired the ability of CL316,243 (β3-agonist) to promote lipolysis in these cells. In contrast, AOAA and PAG had the opposite effect. Taken together, we show that the H 2S-synthesising enzymes CBS, CSE and 3-MST are endogenously expressed during adipogenesis and that both endogenous and exogenous H 2S modulate adipogenesis and adipocyte maturation. 相似文献
10.
Long-time glucocorticoids (GCs) usage causes osteoporosis. In the present study, we explored the potential role of hydrogen sulfide (H 2S) against dexamethasone (Dex)-induced osteoblast cell damage, and focused on the underlying mechanisms. We showed that two H 2S-producing enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), were significantly downregulated in human osteonecrosis tissues as well as in Dex-treated osteoblastic MC3T3-E1 cells. H 2S donor NaHS as well as the CBS activator S-adenosyl-l-methionine (SAM) inhibited Dex-induced viability reduction, death and apoptosis in MC3T3-E1 cells. NaHS activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling, which participated its cyto-protective activity. AMPK inhibition by its inhibitor (compound C) or reduction by targeted-shRNA suppressed its pro-survival activity against Dex in MC3T3-E1 cells. Further, we found that NaHS inhibited Dex-mediated reactive oxygen species (ROS) production and ATP depletion. Such effects by NaHS were again inhibited by compound C and AMPKα1-shRNA. In summary, we show that H 2S inhibits Dex-induced osteoblast damage through activation of AMPK signaling. H 2S signaling might be further investigated as a novel target for anti-osteoporosis treatment. 相似文献
12.
3-mercaptopyruvate sulfurtransferase (3-MST) was a novel hydrogen sulfide (H 2S)-synthesizing enzyme that may be involved in cyanide degradation and in thiosulfate biosynthesis. Over recent years, considerable attention has been focused on the biochemistry and molecular biology of H 2S-synthesizing enzyme. In contrast, there have been few concerted attempts to investigate the changes in the expression of the H 2S-synthesizing enzymes with disease states. To investigate the changes of 3-MST after traumatic brain injury (TBI) and its possible role, mice TBI model was established by controlled cortical impact system, and the expression and cellular localization of 3-MST after TBI was investigated in the present study. Western blot analysis revealed that 3-MST was present in normal mice brain cortex. It gradually increased, reached a peak on the first day after TBI, and then reached a valley on the third day. Importantly, 3-MST was colocalized with neuron. In addition, Western blot detection showed that the first day post injury was also the autophagic peak indicated by the elevated expression of LC3. Importantly, immunohistochemistry analysis revealed that injury-induced expression of 3-MST was partly colabeled by LC3. However, there was no colocalization of 3-MST with propidium iodide (cell death marker) and LC3 positive cells were partly colocalized with propidium iodide. These data suggested that 3-MST was mainly located in living neurons and may be implicated in the autophagy of neuron and involved in the pathophysiology of brain after TBI. 相似文献
14.
Hydrogen sulfide (H 2S) can protect the liver against ischemia-reperfusion (I/R) injury. However, it is unknown whether H 2S plays a role in the protection of hepatic I/R injury in both young and old patients. This study compared the protective effects of H 2S in a rat model (young and old animals) of I/R injury and the mechanism underlying its effects. Young and old rats were assessed following an injection of NaHS. NaHS alone reduced hepatic I/R injury in the young rats by activating the nuclear erythroid-related factor 2 (Nrf2) signaling pathway, but it had little effect on the old rats. NaHS pretreatment decreased miR-34a expression in the hepatocytes of the young rats with hepatic I/R. Overexpresion of miR-34a decreased Nrf-2 and its downstream target expression, impairing the hepatoprotective effect of H 2S on the young rats. More importantly, downregulation of miR-34a expression increased Nrf-2 and the expression of its downstream targets, enhancing the effect of H 2S on hepatic I/R injury in the old rats. This study reveals the different effects of H 2S on hepatic I/R injury in young and old rats and sheds light on the involvement of H 2S in miR-34a modulation of the Nrf-2 pathway. 相似文献
15.
H 2S (hydrogen sulfide), regarded as the third gaseous transmitter, is implicated in ulcerative colitis and colorectal cancers. The present study investigates the effects of H 2S on cell proliferation in human colon cancer HCT 116 cells and SW480 cells. We identified the two key enzymes, CBS and CSE, for H 2S synthesis in HCT 116 cells. An exogenously administered H 2S 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 G 0–G 1 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 p21 Waf1/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 p21 Waf1/Cip1 expression and NO production. The results suggested a role for H 2S in human colonic cancer development. 相似文献
16.
Sleep deprivation (SD) is widespread in society causing serious damage to cognitive function. Hydrogen sulfide (H2S), the third gas signal molecule, plays important regulatory role in learning and memory functions. Inhibition of excessive autophagy and upregulation of silent information regulator 1 (Sirt-1) have been reported to prevent cognitive dysfunction. Therefore, this present work was to address whether H2S attenuates the cognitive impairment induced by SD in Wistar rats and whether the underlying mechanisms involve in inhibition of excessive autophagy and upregulation of Sirt-1. After treatment with SD for 72 h, the cognitive function of Wistar rats was evaluated by Y-maze, new object recognition, object location, and Morris water maze tests. The results shown that SD-caused cognitive impairment was reversed by treatment with NaHS (a donor of H2S). NaHS also prevented SD-induced hippocampal excessive autophagy, as evidenced by the decrease in autophagosomes, the down-regulation of Beclin1, and the up-regulation of p62 in the hippocampus of SD-exposed Wistar rats. Furthermore, Sirtinol, an inhibitor of Sirt-1, reversed the inhibitory roles of NaHS in SD-induced cognitive impairment and excessive hippocampal autophagy in Wistar rats. Taken together, our results suggested that H2S improves the cognitive function of SD-exposed rats by inhibiting excessive hippocampal autophagy in a hippocampal Sirt-1-dependent way. 相似文献
17.
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 (H 2S) has potent antioxidant, anti-inflammatory, and antiapoptotic effects. In this study, we hypothesized that the H 2S 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 H 2S 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 H 2S 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
18.
The mechanism of action of Hydrogen sulfide (H 2S) as a novel endogenous gaseous messenger and potential cardioprotectant is not fully understood. We therefore investigated the prevention of cardiomyocyte apoptosis by exogenous H 2S and the signaling pathways leading to cardioprotection. Using a simulated ischemia–reperfusion (I/Re) model with primary cultured rat neonatal cardiomyocytes, I/Re induced a rapid, time-dependent phosphorylation of c-Jun N-terminal kinase (JNK), with significant elevation at 0.25 h and a peak at 0.5 h during reperfusion. NaHS (H 2S donor) significantly inhibited the early phosphorylation of JNK, especially at 0.5 h. Both NaHS and SP600125 (specific JNK inhibitor) decreased the number of apoptotic cells, lowered cytochrome C release and enhanced Bcl-2 expression. When NaHS application was delayed 1 h after reperfusion, the inhibition of apoptosis by H 2S was negated. In conclusion, this is novel evidence that early JNK inhibition during reperfusion is associated with H 2S-mediated protection against cardiomyocyte apoptosis. 相似文献
19.
Hydrogen sulphide (H 2S) has been shown to play a crucial role in cardiovascular physiology and disease. However, there is no information about the possible role of H 2S in cardiomyocyte hypertrophy (CH). Our results showed that pretreatment with NaHS, an H 2S donor, significantly reduced [ 3H]-leucine incorporation, cell surface area, mRNA expression of brain natriuretic peptide (BNP), intracellular reactive oxygen species (ROS), miR-21 and increased atrial natriuretic peptide (ANP) and miR-133a expression in hypertrophic cardiomyocytes. Anti-miR133a inhibitor transfection partly reduced the anti-hypertrophic effect of NaHS. In conclusion, H 2S is a direct inhibitor of CH; it acts by increasing miR-133a and inhibiting the increase in intracellular ROS. 相似文献
20.
Stress is a common phenomenon that is attracting increasing attention. Hydrogen sulfide (H 2S) is a gasotransmitter that plays an important role in many physiological and pathological events. Our study aimed to estimate the effect and the underlying mechanisms of the H 2S donor, sodium hydrosulfide (NaHS), against immobilization stress (IS)–induced lung injury. Forty adult male rats were classified into control group, NaHS group, and IS groups with and without NaHS treatment. Serum was obtained to determine corticosterone (CORT), total antioxidant capacity (TAC), tumor necrosis factor‐α (TNF‐α), and interleukin-10 (IL-10) levels. Lung H 2S, nitric oxide (NO), inducible nitric oxide synthase (iNOS), and malondialdehyde (MDA) levels were measured. Lung expressions of H 2S synthesizing enzymes and Western blot analysis of nuclear factor erythroid 2–related factor 2 (Nrf2) and hypoxia-inducible factor 1 alpha (HIF 1α) were estimated. Histopathological changes and immunohistochemical assessment of nuclear factor kappa B (NF-κB) and caspase‐3 were also done. Pretreatment with NaHS led to marked histological protection from lung damage seen in IS rats. Furthermore, pretreatment with NaHS before IS protected lung H 2S levels and expressions of H 2S-synthesizing enzymes. Similarly, the levels of CORT, TNF-α, IL-10, MDA, TAC, NO, iNOS, HIF-1 α, and nuclear Nrf2 and expressions of NF-kB and caspase 3 were all maintained at near control levels in contrast to that in the IS rats. In conclusion, NaHS is protective against stress‐induced lung injury due to its antioxidant, anti-inflammatory, anti-fibrotic, and antiapoptotic effects. Thus, NaHS can be used to minimize stress complications on lung. 相似文献
|