scholarly journals Acute Glucose Shift Induces the Activation of the NLRP3 Inflammasome in THP-1 Cells

2021 ◽  
Vol 22 (18) ◽  
pp. 9952
Author(s):  
Ji Yeon Lee ◽  
Yup Kang ◽  
Hae Jin Kim ◽  
Dae Jung Kim ◽  
Kwan Woo Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
P38 Mapk ◽  
Diabetic Complications ◽  
Nlrp3 Inflammasome ◽  
High Glucose ◽  
Glucose Concentration ◽  
Oxygen Species ◽  
Normal Glucose ◽  
Acute Changes

We aimed to investigate the effect of acute glucose shift on the activation of the NLRP3 inflammasome, IL-1β secretion, and underlying signaling pathways in THP-1 cells. THP-1 cells were divided into four groups and exposed to the following glucose concentrations for 24 h: constant normal glucose (NG, 5.5 mM), constant high glucose (HG, 25 mM), normal to high glucose shift (NG-to-HG, 5.5 to 25 mM), and high to normal glucose shift (HG-to-NG, 25 to 5.5 mM). Cell viability, oxidative stress, and the levels of NLRP3 inflammasome components were assessed. Both directions of the acute glucose shift increased the activation of the NLRP3 inflammasome, generation of reactive oxygen species (ROS), and expression of phosphorylated p38 MAPK, JNK, and NF-κB compared with either constant NG or HG. Treatment with N-acetylcysteine, a pharmacological antioxidant, inhibited the acute glucose shift-induced generation of ROS, activation of NLRP3 inflammasome, and upregulation of MAPK-NF-κB. Further analysis using inhibitors of p38 MAPK, JNK, and NF-κB indicated that acute glucose shifts promoted IL-1β secretion by activating the signaling pathway in a ROS-MAPK-NF-κB-NLRP3 inflammasome in THP-1 cells. These findings suggested that acute changes in glucose concentration might cause monocyte inflammation, which is associated with diabetic complications.

Vicenin-2 and scolymoside inhibit high-glucose-induced vascular inflammation in vitro and in vivo

2016 ◽  
Vol 94 (3) ◽  
pp. 287-295 ◽  
Author(s):  
Sae-Kwang Ku ◽  
Jong-Sup Bae
Keyword(s):  
Reactive Oxygen Species ◽  
Vascular Permeability ◽  
Diabetic Complications ◽  
High Glucose ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Vascular Inflammation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Therapeutic Benefits

The vascular inflammatory process has been suggested to play a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, in this study, we attempted to determine whether 2 structurally related flavonoids found in Cyclopia subternata, vicenin-2 and scolymoside, can suppress high-glucose (HG)-induced vascular inflammatory processes in human umbilical vein endothelial cells (HUVECs) and mice. The effects of vicenin-2 and scolymoside on HG-induced vascular inflammation were determined by measuring vascular permeability, leukocyte adhesion and migration, cell adhesion molecule (CAM) expression levels, and reactive oxygen species (ROS) formation. In addition, the anti-inflammation mechanism was investigated using immunofluorescence staining and Western blotting. The data showed that HG markedly increased vascular permeability, monocyte adhesion, expression of CAMs, formation of reactive oxygen species (ROS), and activation of nuclear factor (NF)-κB. Remarkably, pretreatment with vicenin-2 and scolymoside attenuated all of the above-mentioned vascular inflammatory effects of HG. HG-induced vascular inflammatory responses are critical events underlying the development of various diabetic complications; therefore, our results suggest that vicenin-2 and scolymoside have significant therapeutic benefits against diabetic complications and atherosclerosis.

scholarly journals High Potency of a Novel Resveratrol Derivative, 3,3′,4,4′-Tetrahydroxy-trans-stilbene, against Ovarian Cancer Is Associated with an Oxidative Stress-Mediated Imbalance between DNA Damage Accumulation and Repair

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Justyna Mikuła-Pietrasik ◽  
Patrycja Sosińska ◽  
Marek Murias ◽  
Marcin Wierzchowski ◽  
Marta Brewińska-Olchowik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Ovarian Cancer ◽  
Dna Damage ◽  
P38 Mapk ◽  
Cancer Cell ◽  
Damage Accumulation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Stress Dependent

We explored the effect of a new resveratrol (RVT) derivative, 3,3′,4,4′-tetrahydroxy-trans-stilbene (3,3′,4,4′-THS), on viability, apoptosis, proliferation, and senescence of three representative lines of ovarian cancer cells, that is, A2780, OVCAR-3, and SKOV-3,in vitro. In addition, the mechanistic aspects of 3,3′,4,4′-THS activity, including cell redox homeostasis (the production of reactive oxygen species, activity of enzymatic antioxidants, and magnitude of DNA damage accumulation and repair), and the activity of caspases (3, 8, and 9) and p38 MAPK were examined. The study showed that 3,3′,4,4′-THS affects cancer cell viability much more efficiently than its parent drug. This effect coincided with increased generation of reactive oxygen species, downregulated activity of superoxide dismutase and catalase, and excessive accumulation of 8-hydroxy-2′-deoxyguanosine and its insufficient repair due to decreased expression of DNA glycosylase I. Cytotoxicity elicited by 3,3′,4,4′-THS was related to increased incidence of apoptosis, which was mediated by caspases 3 and 9. Moreover, 3,3′,4,4′-THS inhibited cancer cell proliferation and accelerated senescence, which was accompanied by the activation of p38 MAPK. Collectively, our findings indicate that 3,3′,4,4′-THS may constitute a valuable tool in the fight against ovarian malignancy and that the anticancer capabilities of this stilbene proceed in an oxidative stress-dependent mechanism.

scholarly journals Intermittent high glucose exacerbates the aberrant production of adiponectin and resistin through mitochondrial superoxide overproduction in adipocytes

2010 ◽  
Vol 44 (3) ◽  
pp. 179-185 ◽  
Author(s):  
Jiazhong Sun ◽  
Yancheng Xu ◽  
Haohua Deng ◽  
Suxin Sun ◽  
Zhe Dai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Glycemic Variability ◽  
Oxygen Species ◽  
Oxidative Stress Parameter ◽  
Mitochondrial Superoxide ◽  
Transport Chain ◽  
Intermittent High Glucose ◽  
Normal Glucose ◽  
Chain Level

Hypoadiponectinemia and hyperresistinemia may be important in mediating signals from adipocytes to insulin-sensitive tissue and vasculature. However, the mechanism that mediates the aberrant production of adipokines remains poorly understood. In this study, we have investigated the effect of intermittent high glucose on the expression of adiponectin and resistin, and the production of 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine in the adipocytes, either in the presence or in the absence of Mn(III) tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) or thenoyltrifluoroacetone (TTFA). 3T3-L1 adipocytes were incubated for 72 h in media containing different glucose concentrations: 5 mmol/l, 20 mmol/l, 5 mmol/l alternating with 20 mmol/l glucose, with or without MnTBAP and TTFA. We measured the expression of resistin and adiponectin. The production of nitrotyrosine and 8-OHdG as oxidative stress parameter was measured. Both constant and intermittent high glucose significantly suppressed the expression and secretion of adiponectin, and increased expression and secretion of resistin in mature adipocytes compared to normal glucose conditions. However, these effects were significantly greater under intermittent high glucose conditions compared to constant high glucose. The levels of nitrotyrosine and 8-OHdG were significantly elevated under both intermittent and constant high glucose conditions, the effect being greater under intermittent high glucose. In addition, the antioxidants MnTBAP or TTFA reversed the aberrant production of adiponectin and resistin, as well as overproduction of nitrotyrosine and 8-OHdG in adipocytes induced by constant or intermittent high glucose. Intermittent high glucose exacerbates the aberrant production of adiponectin and resistin through reactive oxygen species overproduction at the mitochondrial transport chain level in adipocytes, indicating that glycemic variability has important pathological effects on the secretion of adipokines.

scholarly journals Polyol pathway: A possible mechanism of diabetes complications in the eye

2015 ◽  
Vol 74 (1) ◽  
Author(s):  
Solani D. Mathebula
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Reactive Oxygen Species ◽  
Aldose Reductase ◽  
Diabetic Complications ◽  
Reactive Oxygen ◽  
Crystalline Lens ◽  
Polyol Pathway ◽  
Oxygen Species ◽  
Serum Factors

In complex diseases such as diabetes mellitus, the causative agents include various serum factors such as glucose, aldose reductase, oxygen-free radicals, advanced glycation end products, protein kinase-C and growth factors. The polyol pathway is a pathway of glucose metabolism and is regarded as an important element in the pathogenesis of refractive changes, cataract formation and diabetic retinopathy in individuals with diabetes mellitus. The focus of this review is on the role of the polyol pathway in the pathogenesis of diabetic complications in the eye. The first enzyme (aldose reductase) in the polyol pathway reduces glucose to sorbitol. The second enzyme (sorbitol dehydrogenase) converts sorbitol to fructose. The accumulation of sorbitol and fructose in the crystalline lens and retina leads to the generation of oxidative stress. Oxidative stress is the imbalance between levels of reactive oxygen species and the antioxidant defence in a biological system, and it results in tissue damage. How hyperglycaemia leads to oxidative stress is not clear but could be through a combination of increased levels of reactive oxygen species and decreased capacity of the cellular antioxidant system. Oxidative stress causes the development of diabetic complications that are seen clinically.

scholarly journals Protein-Bound Uremic Toxins Induce Reactive Oxygen Species-Dependent and Inflammasome-Mediated IL-1β Production in Kidney Proximal Tubule Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1326
Author(s):  
Milos Mihajlovic ◽  
Merle M. Krebber ◽  
Yi Yang ◽  
Sabbir Ahmed ◽  
Valeria Lozovanu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Proximal Tubule ◽  
Nlrp3 Inflammasome ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Proximal Tubule Cells ◽  
Caspase 1 ◽  
Tubule Cells

Protein bound-uremic toxins (PBUTs) are not efficiently removed by hemodialysis in chronic kidney disease (CKD) patients and their accumulation leads to various co-morbidities via cellular dysfunction, inflammation and oxidative stress. Moreover, it has been shown that increased intrarenal expression of the NLRP3 receptor and IL-1β are associated with reduced kidney function, suggesting a critical role for the NLRP3 inflammasome in CKD progression. Here, we evaluated the effect of PBUTs on inflammasome-mediated IL-1β production in vitro and in vivo. Exposure of human conditionally immortalized proximal tubule epithelial cells to indoxyl sulfate (IS) and a mixture of anionic PBUTs (UT mix) increased expression levels of NLRP3, caspase-1 and IL-1β, accompanied by a significant increase in IL-1β secretion and caspase-1 activity. Furthermore, IS and UT mix induced the production of intracellular reactive oxygen species, and caspase-1 activity and IL-1β secretion were reduced in the presence of antioxidant N-acetylcysteine. IS and UT mix also induced NF-κB activation as evidenced by p65 nuclear translocation and IL-1β production, which was counteracted by an IKK inhibitor. In vivo, using subtotal nephrectomy CKD rats, a significant increase in total plasma levels of IS and the PBUTs, kynurenic acid and hippuric acid, was found, as well as enhanced urinary malondialdehyde levels. CKD kidney tissue showed an increasing trend in expression of NLRP3 inflammasome components, and a decreasing trend in superoxide dismutase-1 levels. In conclusion, we showed that PBUTs induce inflammasome-mediated IL-1β production in proximal tubule cells via oxidative stress and NF-κB signaling, suggesting their involvement in disease-associated inflammatory processes.

scholarly journals Evaluation of apocynin in vitro on high glucose-induced oxidative stress on tenocytes

2020 ◽  
Vol 9 (1) ◽  
pp. 23-28
Author(s):  
Takashi Kurosawa ◽  
Yutaka Mifune ◽  
Atsuyuki Inui ◽  
Hanak Nishimoto ◽  
Yasuhiro Ueda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Proliferation ◽  
Mrna Expression ◽  
High Glucose ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Control Group ◽  
Oxygen Species

Aims The purpose of this study was to evaluate the in vitro effects of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and a downregulator of intracellular reactive oxygen species (ROS), on high glucose-induced oxidative stress on tenocytes. Methods Tenocytes from normal Sprague-Dawley rats were cultured in both control and high-glucose conditions. Apocynin was added at cell seeding, dividing the tenocytes into four groups: the control group; regular glucose with apocynin (RG apo+); high glucose with apocynin (HG apo+); and high glucose without apocynin (HG apo–). Reactive oxygen species production, cell proliferation, apoptosis and messenger RNA (mRNA) expression of NOX1 and 4, and interleukin-6 (IL-6) were determined in vitro. Results Expression of NOX1, NOX4, and IL-6 mRNA in the HG groups was significantly higher compared with that in the RG groups, and NOX1, NOX4, and IL-6 mRNA expression in the HG apo+ group was significantly lower compared with that in the HG apo– group. Cell proliferation in the RG apo+ group was significantly higher than in the control group and was also significantly higher in the HG apo+ group than in the HG apo– group. Both the ROS accumulation and the amounts of apoptotic cells in the HG groups were greater than those in the RG groups and were significantly less in the HG apo+ group than in the HG apo– group. Conclusion Apocynin reduced ROS production and cell death via NOX inhibition in high-glucose conditions. Apocynin is therefore a potential prodrug in the treatment of diabetic tendinopathy. Cite this article: Bone Joint Res 2020;9(1):23–28.

scholarly journals Proteasome Inhibition Induces Glutathione Synthesis and Protects Cells from Oxidative Stress

2006 ◽  
Vol 282 (7) ◽  
pp. 4364-4372 ◽  
Author(s):  
Noriyuki Yamamoto ◽  
Hideyuki Sawada ◽  
Yasuhiko Izumi ◽  
Toshiaki Kume ◽  
Hiroshi Katsuki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Parkinson Disease ◽  
P38 Mapk ◽  
Proteasome Inhibitors ◽  
Reactive Oxygen ◽  
Proteasome Inhibition ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Glutathione Synthesis

The cause of selective dopaminergic neuronal degeneration in Parkinson disease has still not been resolved, but it has been hypothesized that oxidative stress and the ubiquitin-proteasome system are important in the pathogenesis. In this report, we investigated the effect of proteasome inhibition on oxidative stress-induced cytotoxicity in PC12 cells, an in vitro model of Parkinson disease. Treatment with proteasome inhibitors provided significant protection against toxicity by 6-hydroxydopamine and H2O2 in a concentration-dependent manner. The measurement of intracellular reactive oxygen species using 2′,7′-dichlorofluorescein diacetate demonstrated that lactacystin, a proteasome inhibitor, significantly reduced 6-hydroxydopamineand H2O2-induced reactive oxygen species production. Proteasome inhibitors elevated the amount of glutathione and phosphorylated p38 mitogen-activated protein kinase (MAPK) prior to glutathione elevation. The treatment with lactacystin induced the nuclear translocation of NF-E2-related factor 2 (Nrf2) and increased the level of mRNA for γ-glutamylcysteine synthetase, a rate-limiting enzyme in glutathione synthesis. Furthermore, SB203580, an inhibitor of p38 MAPK, abolished glutathione elevation and cytoprotection by lactacystin. These data suggest that proteasome inhibition afforded cytoprotection against oxidative stress by the elevation of glutathione content, and its elevation was mediated by p38 MAPK phosphorylation.

scholarly journals Characterization of TGF-β by Induced Oxidative Stress in Human Trabecular Meshwork Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 107
Author(s):  
Hsin-Yi Chen ◽  
Hsiu-Chuan Chou ◽  
Yi-Jung Ho ◽  
Shing-Jyh Chang ◽  
En-Chi Liao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
P38 Mapk ◽  
Trabecular Meshwork ◽  
Protein Level ◽  
Critical Role ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Trabecular Meshwork Cells ◽  
Tgf Β1

Oxidative stress generated by reactive oxygen species (ROS) plays a critical role in the pathomechanism of glaucoma, which is a multifactorial blinding disease that may cause irreversible damage within human trabecular meshwork cells (HTMCs). It is known that the transforming growth factor-β (TGF-β) signaling pathway is an important component of oxidative stress-induced damage related to extracellular matrix (ECM) fibrosis and activates cell antioxidative mechanisms. To elucidate the dual potential roles and regulatory mechanisms of TGF-β in effects on HTMCs, we established an in vitro oxidative model using hydrogen peroxide (H2O2) and further focused on TGF-β-related oxidative stress pathways and the related signal transduction. Via a series of cell functional qualitative analyses to detect related protein level alterations and cell fibrosis status, we illustrated the role of TGF-β1 and TGF-β2 in oxidative stress-induced injury by shTGF-β1 and shTGF-β2 knockdown or added recombinant human TGF-β1 protein (rhTGF-β1). The results of protein level showed that p38 MAPK, TGF-β, and its related SMAD family were activated after H2O2 stimulation. Cell functional assays showed that HTMCs with H2O2 exposure duration had a more irregular actin architecture compared to normal TM cells. Data with rhTGF-β1 (1 ng/mL) pretreatment reduced the cell apoptosis rate and amount of reactive oxygen species (ROS), while it also enhanced survival. Furthermore, TGF-β1 and TGF-β2 in terms of antioxidant signaling were related to the activation of collagen I and laminin, which are fibrosis-response proteins. Succinctly, our study demonstrated that low concentrations of TGF-β1 (1 ng/mL) preserves HTMCs from free radical-mediated injury by p-p38 MAPK level and p-AKT signaling balance, presenting a signaling transduction mechanism of TGF-β1 in HTMC oxidative stress-related therapies.

Sign in / Sign up

Export Citation Format

Share Document