scholarly journals Melatonin Inhibits Annulus Fibrosus Cell Senescence through Regulating the ROS/NF-κB Pathway in an Inflammatory Environment

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Jing Li ◽  
Jianghua Li ◽  
Chengzhang Cao ◽  
Jianhua Sun ◽  
Sibo Wang ◽  
...  
Keyword(s):  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Underlying Mechanism ◽  
Telomerase Activity ◽  
Cell Senescence ◽  
Oxygen Species ◽  
Protective Effects ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Inflammation response is an important reason for disc cell senescence during disc degeneration. Recently, melatonin is suggested to protect against disc degeneration. However, the effects of melatonin on annulus fibrosus (AF) cell senescence are not fully studied. The main purpose of this study was to investigate the effects of melatonin on AF cell senescence in an inflammatory environment and the underlying mechanism. Rat disc AF cells were cultured in a medium with tumor necrosis factor-α (TNF-α). Melatonin was added along with the medium to observe its protective effects. Compared with the control AF cells, TNF-α significantly declined cell proliferation potency and telomerase activity, elevated senescence-associated β-galactosidase (SA-β-Gal) activity, upregulated protein expression of senescence markers (p16 and p53), and increased reactive oxygen species (ROS) content and activity of the NF-κB pathway. However, when the TNF-α-treated AF cells were incubated with melatonin, ROS content and activity of the NF-κB pathway were decreased, and those parameters reflecting cell senescence indicated that AF cell senescence was also partly alleviated. Together, melatonin suppresses AF cell senescence through regulating the ROS/NF-κB pathway in an inflammatory environment. This study sheds a new light that melatonin may be promising to retard inflammation-caused disc degeneration.

Natural limonoids protect mice from alcohol-induced liver injury

2020 ◽  
Vol 31 (5) ◽  
Author(s):  
Abacuc Valansa ◽  
Borris Rosnay Tietcheu Galani ◽  
Pascal Dieudonne Djamen Chuisseu ◽  
Armelle Tontsa Tsamo ◽  
Vincent Brice Ayissi Owona ◽  
...  
Keyword(s):  
Liver Injury ◽  
Positive Control ◽  
Negative Control ◽  
Protective Effects ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Different Doses ◽  
Better Than

AbstractBackgroundAlcoholic liver disease (ALD) is regarded as a global health problem with limited therapeutic options. Previous studies highlighted some anticancer, antiviral, and hepatoprotective activities of limonoids, but the effects of these compounds on ALD remain unknown. The present study aimed to evaluate the effect of some natural limonoids on ethanol-induced liver injury.MethodsThirty-five albino mice (Mus musculus) were administered with 40% ethanol in the presence or absence of the different limonoids [including three havanensin-type limonoids, TS1, TS3, Rubescin D isolated from an African medicinal plant, Trichilia rubescens Oliv. (Meliaceae), and one limonin], or silymarin at 50 mg/kg for 3 days. Thereafter, the effect of the most active compound was evaluated in a chronic model of ALD. For this purpose, 24 mice with each group consisting of six mice were administered orally with 40% ethanol and limonoid at different doses (50, 75, and 100 mg/kg) for 28 days. Finally, biochemical parameters such as alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), triglyceride (TG), and tumor necrosis factor α (TNF-α) levels were quantified in liver homogenates.ResultsAll tested limonoids significantly (p < 0.01) reduced ALT levels relative to the negative control in the acute model. However, in comparison to other limonoids, limonin at 50 and 75 mg/kg significantly reduced TG, MDA, and TNF-α levels (1.8-fold); alleviated leukocyte infiltration in liver tissue; significantly increased the activity of SOD; and decreased those of CAT better than silymarin used as a positive control at 50 mg/kg.ConclusionsThese data suggest that limonin possesses protective effects on long-term alcohol poisoning partially due to antioxidant and anti-inflammatory mechanisms.

NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF-α

2004 ◽  
Vol 286 (1) ◽  
pp. L37-L48 ◽  
Author(s):  
Nancy Gertzberg ◽  
Paul Neumann ◽  
Victor Rizzo ◽  
Arnold Johnson
Keyword(s):  
Antisense Oligonucleotide ◽  
Oxygen Species ◽  
Text Generation ◽  
Barrier Dysfunction ◽  
Acetoxymethyl Ester ◽  
Endothelial Barrier Dysfunction ◽  
Endothelial Monolayers ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

We tested the hypothesis that the NAD(P)H oxidase-dependent generation of superoxide anion ([Formula: see text]) mediates tumor necrosis factor-α (TNF)-induced alterations in the permeability of pulmonary microvessel endothelial monolayers (PMEM). The permeability of PMEM was assessed by the clearance rate of Evans blue-labeled albumin. The NAD(P)H oxidase subcomponents p47phoxand p22phoxwere assessed by immunofluorescent microscopy and Western blot. The reactive oxygen species [Formula: see text] was measured by the fluorescence of 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetatedi(acetoxymethyl ester), 5 (and 6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate-acetyl ester, and dihydroethidium. TNF treatment (50 ng/ml for 4.0 h) induced 1) p47phoxtranslocation, 2) an increase in p22phoxprotein, 3) increased localization of p47phoxwith p22phox, 4) [Formula: see text] generation, and 5) increased permeability to albumin. p22phoxantisense oligonucleotide prevented the TNF-induced effect on p22phox, p47phox, [Formula: see text], and permeability. The scrambled nonsense oligonucleotide had no effect. The TNF-induced increase in [Formula: see text] and permeability to albumin was also prevented by the [Formula: see text] scavenger Cu-Zn superoxide dismutase (100 U/ml). The results indicate that the activation of NAD(P)H oxidase, via the generation of [Formula: see text], mediates TNF-induced barrier dysfunction in PMEM.

scholarly journals Extensive mechanical tension promotes annulus fibrosus cell senescence through suppressing cellular autophagy

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Liang Zhao ◽  
Baofang Tian ◽  
Qing Xu ◽  
Cunxin Zhang ◽  
Luo Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Expression ◽  
Disc Degeneration ◽  
Cell Biology ◽  
Annulus Fibrosus ◽  
Mechanical Load ◽  
Telomerase Activity ◽  
Cell Senescence ◽  
Mechanical Tension ◽  
Cellular Autophagy

Abstract Background: Mechanical load contributes a lot to the initiation and progression of disc degeneration. Annulus fibrosus (AF) cell biology under mechanical tension remains largely unclear. Objective: The present study was aimed to investigate AF cell senescence under mechanical tension and the potential role of autophagy. Methods: Rat AF cells were cultured and experienced different magnitudes (5% elongation and 20% elongation) of mechanical tension for 12 days. Control AF cells were kept static. Cell proliferation, telomerase activity, cell cycle fraction, and expression of senescence-related molecules (p16 and p53) and matrix macromolecules (aggrecan and collagen I) were analyzed to evaluate cell senescence. In addition, expression of Beclin-1 and LC3, and the ratio of LC3-II to LC3-I were analyzed to investigate cell autophagy. Results: Compared with the control group and 5% tension group, 20% tension group significantly decreased cell proliferation potency and telomerase activity, increased G1/G0 phase fraction, and up-regulated gene/protein expression of p16 and p53, whereas down-regulated gene/protein expression of aggrecan and collagen I. In addition, autophagy-related parameters such as gene/protein expression of Beclin-1 and LC3, and the ratio of LC3-II to LC3-I, were obviously suppressed in the 20% tension group. Conclusion: High mechanical tension promotes AF cell senescence though suppressing cellular autophagy. The present study will help us to better understand AF cell biology under mechanical tension and mechanical load-related disc degeneration.

scholarly journals Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats

2021 ◽  
Vol 16 (1) ◽  
pp. 128-141
Author(s):  
Gang Xiao ◽  
Mei Zhang ◽  
Xing Peng ◽  
Guangyuan Jiang
Keyword(s):  
Signaling Pathways ◽  
Cerebral Aneurysm ◽  
Protocatechuic Acid ◽  
Inflammatory Responses ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Our current research aims to examine whether protocatechuic acid (PCA) can be used as a therapeutic agent for the development of cerebral aneurysm (CA) and to elucidate the mechanisms behind this. We assessed the effects of PCA at 50 and 100 mg/kg on the activation of signaling pathways for tissue necrosis factor (TNF)-α/nuclear factor (NF)-κB/nuclear factor erythroid 2 (Nrf-2) on progression and development in an elastase-induced CA model, accompanied by a high-salt diet to induce hypertension. The expression of inflammatory cytokines, chemokines, tumor necrosis factor-α, interleukins (IL)-8, IL-17, IL-6, IL-1β, and matrix metalloproteinase (MMP)-2 and MMP-9 was analyzed by ELISA, western blot, and reverse transcriptase quantative polymerase chain reaction. The expression levels of antioxidant enzymes and translocation of Nrf-2 were also determined. The group treated with PCA demonstrated a significant (P < 0.05) decrease in the aneurysmal size in rats compared to the CA-induced group. We found that PCA treatment suppressed the invasion of macrophage and activation of TNF-α/NF-κB/Nrf-2 signaling pathways. There was a significant decrease (P < 0.05) in pro-inflammatory cytokine and chemokine levels in a dose-dependent manner. We found that PCA treatment exerts protective effects by suppressing the development and progression of CA through the inhibition of inflammatory responses in macrophages via TNF-α/NF-κB/Nrf-2 signaling pathways, thus demonstrating that PCA can act as a treatment for CA.

Modulation of the Activation of Extracellular Signal-Regulated Kinase (ERK) and the Production of Inflammatory Mediators by ADP-Ribosylation Inhibitors

2003 ◽  
Vol 384 (10-11) ◽  
pp. 1509-1513 ◽  
Author(s):  
C. Le Page ◽  
J. Wietzerbin
Keyword(s):  
Inflammatory Mediators ◽  
Nuclear Factor Κb ◽  
Oxygen Species ◽  
Extracellular Signal Regulated Kinase ◽  
Adp Ribosylation ◽  
Raw264.7 Macrophages ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract ADP-ribosylation is involved in nuclear factor κB (NF-κB)-dependent gene expression induced by lipopolysaccharide in murine macrophages. Here we have investigated the mechanism by which ADP-ribosylation inhibitors block signaling pathways induced in macrophages. In RAW264.7 macrophages the inducers of NF-κB activate the production of reactive oxygen species and three mitogenactivated protein kinases (MAPK), the extracellular signal regulated kinase (ERK), the c-jun N-terminal kinase/stress-activated protein kinase (JNK), and p38. We demonstrate that ADP-ribosylation inhibitors specifically inhibit ERK MAPK activation and reduce the release of inflammatory mediators such as tumor necrosis factor α (TNF-α), IL-6 and nitrite.

scholarly journals Kaempferol Attenuates LPS-Induced Striatum Injury in Mice Involving Anti-Neuroinflammation, Maintaining BBB Integrity, and Down-Regulating the HMGB1/TLR4 Pathway

2019 ◽  
Vol 20 (3) ◽  
pp. 491 ◽  
Author(s):  
Ying-Lin Yang ◽  
Xiao Cheng ◽  
Wei-Han Li ◽  
Man Liu ◽  
Yue-Hua Wang ◽  
...  
Keyword(s):  
Protective Effects ◽  
Neuroprotective Effects ◽  
Chemotactic Protein ◽  
Tnf Α ◽  
Factor Α ◽  
Cell Adhesion Molecule 1 ◽  
Neuron Injury ◽  
Intercellular Cell Adhesion Molecule ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Neuroinflammation has been demonstrated to be linked with Parkinson’s disease (PD), Alzheimer’s disease, and cerebral ischemia. Our previous investigation had identified that kaempferol (KAE) exerted protective effects on cortex neuron injured by LPS. In this study, the effects and possible mechanism of KAE on striatal dopaminergic neurons induced by LPS in mice were further investigated. The results showed that KAE improved striatal neuron injury, and increased the levels of tyrosine hydroxylase (TH) and postsynaptic density protein 95 (PSD95) in the striatum of mice. In addition, KAE inhibited the production of pro-inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), reduced the level of monocyte chemotactic protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1), and cyclooxygenase-2 (COX-2) in the striatum tissues. Furthermore, KAE protected blood-brain barrier (BBB) integrity and suppressed the activation of the HMGB1/TLR4 inflammatory pathway induced by LPS in striatum tissues of mice. In conclusion, these results suggest that KAE may have neuroprotective effects against striatum injury that is induced by LPS and the possible mechanisms are involved in anti-neuroinflammation, maintaining BBB integrity, and down-regulating the HMGB1/TLR4 pathway.

scholarly journals Catalase Enhances Viability of Human Chondrocytes in Culture by Reducing Reactive Oxygen Species and Counteracting Tumor Necrosis Factor-α-Induced Apoptosis

2018 ◽  
Vol 49 (6) ◽  
pp. 2427-2442 ◽  
Author(s):  
Siming Li ◽  
Xiaohong Yang ◽  
Zhencheng Feng ◽  
Pengzhen Wang ◽  
Weicong Zhu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Oxygen Species ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

Background/Aims: Both physiologic remodeling and pathologic regeneration of cartilage tissue rely upon chondrocyte functions and are benefited from factors that promote viability and inhibit apoptosis of the cell, and associated mechanisms. High level of reactive oxygen species (ROS) and proinflammatory cytokines activate apoptosis signaling and initiate cell death, which can be attenuated by antioxidants. This study examined the effect of catalase (CAT) on ROS and tumor necrosis factor-α (TNF-α)-induced apoptosis in human C28/I2 chondrocytes cultured in monolayer. Methods: Chondrocytes were treated with diluted CAT in the presence or absence of TNF-α and compared to untreated cells. Levels of hydrogen peroxide (H2O2) and mitochondrial membrane potential (Δψm) were measured using fluorescent labeling, cell apoptosis was assayed by flow cytometry using Annexin V/propidium iodide (PI) staining, gene expression was detected by quantitative real time polymerase chain reaction (qRT-PCR) and the proteins were investigated by Western blotting. Results: CAT effectively reduced the intracellular ROS caused by the monolayer culture system, enhanced the Δψm depending on the presence of TNF-α and promoted morphological features at sub-cellular level. CAT also attenuated the TNF-α-upregulated expression of factors/mediators of extrinsic cell death cascade and apoptotic caspases, ultimately resulted in promoted cellular viability. Conclusion: The anti-apoptotic effect of CAT on chondrocytes via scavenging ROS and suppressing TNF-α-induced cell apoptosis by TNF/TNF receptor (TNFR) mediated death signaling pathway and potentiate CAT as a complementary agent beneficial to cartilage remodeling and regeneration in vivo, and cell-based therapies of cartilage repair demanding viable cells expanded ex vivo.

scholarly journals Deletion of MicroRNA-144/451 Cluster Aggravated Brain Injury in Intracerebral Hemorrhage Mice by Targeting 14-3-3ζ

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaohong Wang ◽  
Yin Hong ◽  
Lei Wu ◽  
Xiaochun Duan ◽  
Yue Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intracerebral Hemorrhage ◽  
Gene Knockout ◽  
Underlying Mechanism ◽  
Neurological Deficits ◽  
Tnf Α ◽  
Collagenase Injection ◽  
Factor Α ◽  
The Brain ◽  
Necrosis Factor

This study aims at evaluating the importance and its underlying mechanism of the cluster of microRNA-144/451 (miR-144/451) in the models with intracerebral hemorrhage (ICH). A model of collagenase-induced mice with ICH and a model of mice with simple miR-144/451 gene knockout (KO) were used in this study. Neurodeficits and the water content of the brain of the mice in each group were detected 3 days after collagenase injection. The secretion of proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), as well as certain biomarkers of oxidative stress, was determined in this study. The results revealed that the expression of miR-451 significantly decreased in the mice with ICH, whereas miR-144 showed no significant changes. KO of the cluster of miR-144/451 exacerbated the neurological deficits and brain edema in the mice with ICH. Further analyses demonstrated that the KO of the cluster of miR-144/451 significantly promoted the secretion of TNF-α and IL-1β and the oxidative stress in the perihematomal region of the mice with ICH. In addition, the miR-144/451's depletion inhibited the regulatory axis' activities of miR-451-14-3-3ζ-FoxO3 in the mice with ICH. In conclusion, these data demonstrated that miR-144/451 might protect the mice with ICH against neuroinflammation and oxidative stress by targeting the pathway of miR-451-14-3-3ζ-FoxO3.

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