scholarly journals Hydrogen Sulfide Inhibits High Glucose-Induced sFlt-1 Production via Decreasing ADAM17 Expression in 3T3-L1 Adipocytes

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Tian-xiao Hu ◽  
Gang Wang ◽  
Wei Wu ◽  
Lu Gao ◽  
Qing-ying Tan ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
High Glucose ◽  
Vascular Complications ◽  
Signaling Molecule ◽  
Sodium Hydrosulfide ◽  
Diabetic Vascular Complications ◽  
Subsequent Decrease ◽  
Therapeutic Value

Hydrogen sulfide (H2S) has recently been identified as an endogenous gaseous signaling molecule. The aim of the present study was to investigate the effect of H2S on high glucose- (HG-) induced ADAM17 expression and sFlt-1 production in 3T3-L1 adipocytes. Firstly, we found that HG DMEM upregulated the expression of ADAM17 and production of sFlt-1 in 3T3-L1 adipocytes. Knocking down ADAM17 attenuated the effect of high glucose on sFlt-1 production in adipocytes. HG decreased the expression of CSE and 3-MST, as well as the endogenous H2S production. Furthermore, knocking down CSE and 3-MST significantly increased ADAM17 expression and sFlt-1 production. The addition of exogenous H2S through the administration of sodium hydrosulfide (NaHS) inhibited HG-induced upregulation of ADAM17 expression and sFlt-1 production. In conclusion, decreased expression of CSE and 3-MST and the subsequent decrease in H2S production contribute to high glucose-induced sFlt-1 production via activating ADAM17 in adipocytes. Exogenous H2S donor NaHS has a potential therapeutic value for diabetic vascular complications.

Icariin Attenuates High Glucose-Induced Apoptosis, Oxidative Stress, and Inflammation in Human Umbilical Venous Endothelial Cells

Planta Medica ◽  
2019 ◽  
Vol 85 (06) ◽  
pp. 473-482 ◽  
Author(s):  
Si Sun ◽  
Le Liu ◽  
Xiaojun Tian ◽  
Yanghongyun Guo ◽  
Yingkang Cao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
High Glucose ◽  
Vascular Endothelial Cells ◽  
Reactive Oxygen Species Generation ◽  
Vascular Complications ◽  
Flavonoid Glycoside ◽  
Inflammatory Factors ◽  
Diabetic Vascular Complications ◽  
Induced Apoptosis

AbstractEndothelial dysfunction is closely associated with diabetic complications. Icariin, a flavonoid glycoside isolated from the Epimedium plant species, exhibits antidiabetic properties. However, its impact on endothelial function remains poorly understood, particularly under hyperglycemia. In this study, we investigated the potential protective effect of icariin on high glucose-induced detrimental effects on vascular endothelial cells. Human umbilical venous endothelial cells were incubated in media containing 5.5 mM glucose (normal glucose) or 25 mM glucose (high glucose) in the presence or absence of 50 µM icariin for 72 h. We found that high glucose markedly induced cell apoptosis, enhanced reactive oxygen species generation, and elevated expression levels of inflammatory factors and cell adhesion molecules, which were greatly subdued by icariin supplementation. In conclusion, icariin exerted a beneficial effect on high glucose-induced endothelial dysfunction. This new finding provides a promising strategy for future treatment of diabetic vascular complications.

scholarly journals Hydrogen Sulfide Ameliorates High Glucose-induced Inflammation Through SIRT1-mTOR/NF-κB Signaling Pathway in HT-22 cells

2020 ◽  
Author(s):  
Xinrui Li ◽  
Yinghua Yu ◽  
Peiquan Yu ◽  
Ting Xu ◽  
Jiao Liu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
High Glucose ◽  
Near Infrared ◽  
Neuronal Cell ◽  
Inflammatory Factors ◽  
Sodium Hydrosulfide ◽  
Protein Levels

Abstract Background: Hyperglycemia-induced neuroinflammation promotes the progression of diabetic encephalopathy (DE). Hydrogen sulfide (H2S) exerts anti-inflammatory and neuroprotective activities against neurodegenerative diseases. However, its role in hyperglycemia-induced neuronal inflammation has not been investigated. Herein, we examined the effects and its related signaling pathway of H2S on inflammatory response in high glucose-treated HT-22 cells.Methods: A hippocampal neuronal cell line, HT-22, was used as an in vitro model to explore the function of H2S on inflammatory response triggered by high glucose. A dicyanoisophorone-based near-infrared fluorescent probe (NIR-NP) was synthesized to detect H2S levels in HT-22 cells. Western blotting, immunofluorescence and real time-qPCR were carried out to study the mechanism of action for H2S.Results: We found that high glucose (85 mM) decreased the level of endogenous H2S and the expression of cystathionine-β-synthase (CBS) which is the main enzyme for H2S production in the brain. Sodium hydrosulfide (NaHS, a H2S donor) or S-adenosylmethionine (SAMe, an allosteric activator of CBS) administration restored high glucose-induced downregulation of CBS and H2S levels. Importantly, high glucose upregulated the level of pro-inflammatory factors (IL-1β, IL-6, TNF-α) in HT-22 cells. Treatment with NaHS or SAMe alleviated this enhanced transcription of these pro-inflammatory factors, suggesting that H2S might ameliorate high glucose-induced inflammation in HT-22 cells. We also found that high glucose reduced SIRT1 protein levels. SIRT1 reduction elevated the level of p-mTOR, p-NF-κB and pro-inflammatory factors, which were restored by resveratrol (a SIRT1 agonist). These results suggested that SIRT1 might be an upstream mediator of mTOR/NF-κB signaling pathway. Furthermore, NaHS or SAMe treatment reversed the expression of SIRT1, mTOR and NF-κB under high glucose conditions.Conclusions: Our study revealed that high glucose decreased CBS to reduce the production of H2S, which in turn decreased the expression of SIRT1. The reduction of SIRT1 activated mTOR/NF-κB signaling to promote inflammation. Given that promoting H2S production using NaHS or SAMe can reverse high glucose-induced inflammatory response, our study might shed light on the prophylactic treatment of DE.

Abstract MP250: Reduction In Endothelial Aryl Hydrocarbon Receptor Nuclear Translocator (arnt) Mediates Vascular Dysfunction In Mice With Type 2 Diabetes Mellitus

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Tu Nguyen ◽  
Kaichao Pan ◽  
Maura Knapp ◽  
Mei Zheng ◽  
Nikola Sladojevic ◽  
...  
Keyword(s):  
Cell Viability ◽  
High Glucose ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Tube Formation ◽  
Diabetic Mice ◽  
Aryl Hydrocarbon ◽  
Diabetic Vascular Complications ◽  
High Fat Chow

Background: Endothelial dysfunction, especially at the microvasculature level, is one of the most deleterious events in diabetes. ARNT is a transcription factor that functions as a master regulator of glucose homeostasis, but its role in diabetic vascular complications is poorly understood. Results and method: We found a reduction in ARNT expression in microvascular endothelial cells (MVECs) derived from type 2 diabetic mice (db/db). Thus, we generated an inducible, EC-specific ARNT-knockout mutation ( Arnt ΔEC, ERT2) to address the hypothesis that aberrations in ARNT expression might contribute to the vascular deficiencies associated with diabetes. We show here that loss of ARNT in the endothelium mimics diabetic phenotypes, such as impairs blood flow recovery after hindlimb ischemia, delays wound healing, and exacerbates infiltration of pro-inflammatory neutrophils after myocardial infarction. Interestedly, the degree of these impairments in the KO mice was more remarkable in diabetic animals induced with high-fat chow. In addition, the siRNA-mediated knockdown of ARNT activity reduced tube formation and cell viability measurements in HUVECs cultured under high-glucose conditions. The Arnt ΔEC, ERT2 mutation also reduced measures of cell viability while increasing the production of reactive oxygen species (ROS) in MVECs isolated from mouse skeletal muscle, and the viability of Arnt ΔEC, ERT2 MVECs under high-glucose concentrations increased when the cells were treated with a ROS inhibitor. Conclusion: Collectively, these observations suggest that declines in endothelial ARNT expression contribute to the suppressed angiogenic phenotype in diabetic mice and that the cytoprotective effect of ARNT expression in ECs is at least partially mediated by declines in ROS production. Endothelial ARNT might be a critical mediator of endothelial function and could serve as a therapeutic target for diabetic complications.

scholarly journals Hydrogen Sulfide Promotes Nodulation and Nitrogen Fixation in Soybean–Rhizobia Symbiotic System

2019 ◽  
Vol 32 (8) ◽  
pp. 972-985 ◽  
Author(s):  
Hang Zou ◽  
Ni-Na Zhang ◽  
Qing Pan ◽  
Jian-Hua Zhang ◽  
Juan Chen ◽  
...  
Keyword(s):  
Nitrogen Fixation ◽  
Hydrogen Sulfide ◽  
Glutamate Synthase ◽  
Marker Genes ◽  
Symbiotic System ◽  
Signaling Molecule ◽  
Sodium Hydrosulfide ◽  
Physiological Processes ◽  
Soybean Rhizobia ◽  
Early Nodulin

The rhizobium–legume symbiotic system is crucial for nitrogen cycle balance in agriculture. Hydrogen sulfide (H2S), a gaseous signaling molecule, may regulate various physiological processes in plants. However, whether H2S has regulatory effect in this symbiotic system remains unknown. Herein, we investigated the possible role of H2S in the symbiosis between soybean (Glycine max) and rhizobium (Sinorhizobium fredii). Our results demonstrated that an exogenous H2S donor (sodium hydrosulfide [NaHS]) treatment promoted soybean growth, nodulation, and nitrogenase (Nase) activity. Western blotting analysis revealed that the abundance of Nase component nifH was increased by NaHS treatment in nodules. Quantitative real-time polymerase chain reaction data showed that NaHS treatment upregulated the expressions of symbiosis-related genes nodA, nodC, and nodD of S. fredii. In addition, expression of soybean nodulation marker genes, including early nodulin 40 (GmENOD40), ERF required for nodulation (GmERN), nodulation signaling pathway 2b (GmNSP2b), and nodulation inception genes (GmNIN1a, GmNIN2a, and GmNIN2b), were upregulated. Moreover, the expressions of glutamate synthase (GmGOGAT), asparagine synthase (GmAS), nitrite reductase (GmNiR), ammonia transporter (GmSAT1), leghemoglobin (GmLb), and nifH involved in nitrogen metabolism were upregulated in NaHS-treated soybean roots and nodules. Together, our results suggested that H2S may act as a positive signaling molecule in the soybean–rhizobia symbiotic system and enhance the system’s nitrogen fixation ability.

scholarly journals Upregulation of Periostin Prevents High Glucose-Induced Mitochondrial Apoptosis in Human Umbilical Vein Endothelial Cells via Activation of Nrf2/HO-1 Signaling

2016 ◽  
Vol 39 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Zhi-ying Zhong ◽  
Yu Tang
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Umbilical Vein ◽  
Vascular Complications ◽  
Ros Generation ◽  
Mitochondrial Apoptosis ◽  
Human Umbilical Vein ◽  
Diabetic Vascular Complications ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Background/Aims: High glucose-induced oxidative damage to endothelial cells plays a central role in the pathogenesis of diabetic vascular complications. This study was undertaken to explore the role of periostin in high glucose-induced endothelial cell apoptosis and associated molecular mechanisms. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (33.3 mmol/L) and examined for the expression of periostin. The effects of periostin upregulation on high glucose-induced apoptosis, mitochondrial dysfunction, and reactive oxygen species (ROS) production were determined. The activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) by periostin was checked. HO-1 knockdown experiments were done to confirm its role in the action of periostin in high glucose-exposed HUVECs. Results: High glucose significantly upregulated the expression of periostin in HUVECs. Enforced expression of periostin attenuated high glucose-induced apoptosis in HUVECs, as determined by TUNEL staining and caspase-3 activity assay. Periostin overexpression prevented loss of Δψm, release of mitochondrial cytochrome c, and dysregulation of Bcl-2 and Bax in high glucose-exposed HUVECs. Periostin upregulation suppressed high glucose-induced ROS generation and activated the Nrf2/HO-1 signaling. HO-1 silencing restored high glucose-induced ROS generation and apoptotic response in periostin-overexpressing HUVECs. Conclusion: Periostin mitigates high glucose-induced mitochondrial apoptosis in endothelial cells, via activation of Nrf2/HO-1 signaling and reduction of ROS formation. Further studies are warranted to explore the therapeutic potential of periostin in diabetic vascular complications.

scholarly journals α-Mangostin protects against high-glucose induced apoptosis of human umbilical vein endothelial cells

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Yanli Luo ◽  
Minxiang Lei
Keyword(s):  
High Glucose ◽  
Caspase 3 ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Vascular Complications ◽  
Vascular Endothelial ◽  
Apoptosis Rate ◽  
Diabetic Vascular Complications ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Diabetic vascular complications result from high-glucose induced vascular endothelial cell dysfunction. There is an emerging need for novel drugs with vascular endothelial cell protective effects for the treatment of diabetic vascular complications. The present study aimed to investigate the protective effect of α-mangostin against high-glucose induced apoptosis of cultured human umbilical vein endothelial cells (HUVECs). HUVECs were treated with glucose to induce apoptosis. The expression of the apoptosis-related proteins, Bcl-2, Bax, and cleaved caspase-3, were detected by Western blotting. Ceramide concentration and acid sphingomyelinase (ASM) activity were assayed by HPLC. The cell apoptosis rate was detected by flow cytometry after staining with annexin V/propidium iodide (PI). Compared with HUVECs cultured in 5 mM glucose, cells cultured in 30 mM glucose exhibited a higher apoptosis rate, up-regulation of cleaved caspase-3 and Bax (proapoptotic proteins), down-regulation of Bcl-2 (anti-apoptotic protein), increased ceramide concentration, and enhanced ASM activity (all P<0.05). α-Mangostin (15 µM) significantly attenuated the high-glucose induced increase in apoptosis rate (8.64 ± 2.16 compared with 19.6 ± 3.54%), up-regulation of cleaved caspase-3 and Bax, down-regulation of Bcl-2, elevation of ceramide level, and enhancement of ASM activity (all P<0.05). The effects of desipramine were similar to those of α-mangostin. The protective effect of α-mangostin on high-glucose induced apoptotic damage may be mediated by an inhibition of ASM and thus a decreased level of ceramide.

scholarly journals Hydrogen sulfide promotes nodulation and nitrogen fixation in soybean-rhizobia symbiotic system

2018 ◽  
Author(s):  
Hang Zou ◽  
Ni-Na Zhang ◽  
Qing Pan ◽  
Jian-Hua Zhang ◽  
Juan Chen ◽  
...  
Keyword(s):  
Nitrogen Fixation ◽  
Hydrogen Sulfide ◽  
Glutamate Synthase ◽  
Marker Genes ◽  
Symbiotic System ◽  
Signaling Molecule ◽  
Sodium Hydrosulfide ◽  
Physiological Processes ◽  
Soybean Rhizobia ◽  
Early Nodulin

AbstractThe rhizobium-legume symbiotic system is crucial for nitrogen cycle balance in agriculture. Hydrogen sulfide (H2S), a gaseous signaling molecule, may regulate various physiological processes in plants. However, whether H2S has regulatory effect in this symbiotic system remains unknown. Herein, we investigated the possible role of H2S in the symbiosis between soybean (Glycine max) and rhizobium (Sinorhizobium fredii). Our results demonstrated that exogenous H2S donor (sodium hydrosulfide, NaHS) treatment promoted soybean growth, nodulation and nitrogenase (Nase) activity. Western blotting analysis revealed that the abundance of nitrogenase component nifH was increased by NaHS treatment in nodules. Quantitative real-time PCR data showed that NaHS treatment up-regulated the expressions of symbiosis-related genesnodCandnodDofS. fredii. Besides, expression of soybean nodulation marker genes including early nodulin 40 (GmENOD40), ERF required for nodulation (GmERN), nodulation signaling pathway2b (GmNSP2b) and nodulation inception genes (GmNIN1a, GmNIN2aandGmNIN2b) were up-regulated. Moreover, the expressions of glutamate synthase (GmGS), nitrite reductase (GmNiR), ammonia transporter (GmSAT1), andnifHinvolved in nitrogen metabolism were up-regulated in NaHS-treated soybean roots and nodules. Together, our results suggested that H2S may act as a positive signaling molecule in soybean-rhizobia symbiotic system and enhance their nitrogen fixation ability.HighlightWe demonstrated for the first time that H2S as a signaling molecule may promote the establishment of symbiotic relationship and nitrogen fixation ability in the soybean-rhizobia symbiotic system.

L-carnosine and its Derivatives as New Therapeutic Agents for the Prevention and Treatment of Vascular Complications of Diabetes

2020 ◽  
Vol 27 (11) ◽  
pp. 1744-1763 ◽  
Author(s):  
Stefano Menini ◽  
Carla Iacobini ◽  
Claudia Blasetti Fantauzzi ◽  
Giuseppe Pugliese
Keyword(s):  
Diabetic Nephropathy ◽  
Life Quality ◽  
Vascular Complications ◽  
Carbonyl Stress ◽  
Complications Of Diabetes ◽  
Diabetic Vascular Complications ◽  
Reactive Carbonyl Species ◽  
Stage Renal Disease ◽  
Stress Dependent ◽  
End Stage

Vascular complications are among the most serious manifestations of diabetes. Atherosclerosis is the main cause of reduced life quality and expectancy in diabetics, whereas diabetic nephropathy and retinopathy are the most common causes of end-stage renal disease and blindness. An effective therapeutic approach to prevent vascular complications should counteract the mechanisms of injury. Among them, the toxic effects of Advanced Glycation (AGEs) and Lipoxidation (ALEs) end-products are well-recognized contributors to these sequelae. L-carnosine (β-alanyl-Lhistidine) acts as a quencher of the AGE/ALE precursors Reactive Carbonyl Species (RCS), which are highly reactive aldehydes derived from oxidative and non-oxidative modifications of sugars and lipids. Consistently, L-carnosine was found to be effective in several disease models in which glyco/lipoxidation plays a central pathogenic role. Unfortunately, in humans, L-carnosine is rapidly inactivated by serum carnosinase. Therefore, the search for carnosinase-resistant derivatives of Lcarnosine represents a suitable strategy against carbonyl stress-dependent disorders, particularly diabetic vascular complications. In this review, we present and discuss available data on the efficacy of L-carnosine and its derivatives in preventing vascular complications in rodent models of diabetes and metabolic syndrome. We also discuss genetic findings providing evidence for the involvement of the carnosinase/L-carnosine system in the risk of developing diabetic nephropathy and for preferring the use of carnosinase-resistant compounds in human disease. The availability of therapeutic strategies capable to prevent both long-term glucose toxicity, resulting from insufficient glucoselowering therapy, and lipotoxicity may help reduce the clinical and economic burden of vascular complications of diabetes and related metabolic disorders.

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