scholarly journals Irisin Mitigates Oxidative Stress, Chondrocyte Dysfunction and Osteoarthritis Development through Regulating Mitochondrial Integrity and Autophagy

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 810
Author(s):  
Feng-Sheng Wang ◽  
Chung-Wen Kuo ◽  
Jih-Yang Ko ◽  
Yu-Shan Chen ◽  
Shao-Yu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Dna Damage ◽  
Articular Chondrocytes ◽  
Atp Production ◽  
Knee Oa ◽  
Fibronectin Type Iii ◽  
Cartilage Erosion ◽  
Fibronectin Type Iii Domain ◽  
Muscle Homeostasis

Compromised autophagy and mitochondrial dysfunction downregulate chondrocytic activity, accelerating the development of osteoarthritis (OA). Irisin, a cleaved form of fibronectin type III domain containing 5 (FNDC5), regulates bone turnover and muscle homeostasis. Little is known about the effect of Irisin on chondrocytes and the development of osteoarthritis. This study revealed that human osteoarthritic articular chondrocytes express decreased level of FNDC5 and autophagosome marker LC3-II but upregulated levels of oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG) and apoptosis. Intra-articular administration of Irisin further alleviated symptoms of medial meniscus destabilization, like cartilage erosion and synovitis, while improved the gait profiles of the injured legs. Irisin treatment upregulated autophagy, 8-OHdG and apoptosis in chondrocytes of the injured cartilage. In vitro, Irisin improved IL-1β-mediated growth inhibition, loss of specific cartilage markers and glycosaminoglycan production by chondrocytes. Irisin also reversed Sirt3 and UCP-1 pathways, thereby improving mitochondrial membrane potential, ATP production, and catalase to attenuated IL-1β-mediated reactive oxygen radical production, mitochondrial fusion, mitophagy, and autophagosome formation. Taken together, FNDC5 loss in chondrocytes is correlated with human knee OA. Irisin repressed inflammation-mediated oxidative stress and extracellular matrix underproduction through retaining mitochondrial biogenesis, dynamics and autophagic program. Our analyses shed new light on the chondroprotective actions of this myokine, and highlight the remedial effects of Irisin on OA development.

scholarly journals Phytochemicals from the Cocoa Shell Modulate Mitochondrial Function, Lipid and Glucose Metabolism in Hepatocytes via Activation of FGF21/ERK, AKT, and mTOR Pathways

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 136
Author(s):  
Miguel Rebollo-Hernanz ◽  
Yolanda Aguilera ◽  
Maria A. Martin-Cabrejas ◽  
Elvira Gonzalez de Gonzalez de Mejia
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Cell Model ◽  
Fibroblast Growth Factor 21 ◽  
Alcoholic Fatty Liver ◽  
Atp Production ◽  
Cocoa Shell

The cocoa shell is a by-product that may be revalorized as a source of bioactive compounds to prevent chronic cardiometabolic diseases. This study aimed to investigate the phytochemicals from the cocoa shell as targeted compounds for activating fibroblast growth factor 21 (FGF21) signaling and regulating non-alcoholic fatty liver disease (NAFLD)-related biomarkers linked to oxidative stress, mitochondrial function, and metabolism in hepatocytes. HepG2 cells treated with palmitic acid (PA, 500 µmol L−1) were used in an NAFLD cell model. Phytochemicals from the cocoa shell (50 µmol L−1) and an aqueous extract (CAE, 100 µg mL−1) enhanced ERK1/2 phosphorylation (1.7- to 3.3-fold) and FGF21 release (1.4- to 3.4-fold) via PPARα activation. Oxidative stress markers were reduced though Nrf-2 regulation. Mitochondrial function (mitochondrial respiration and ATP production) was protected by the PGC-1α pathway modulation. Cocoa shell phytochemicals reduced lipid accumulation (53–115%) and fatty acid synthase activity (59–93%) and prompted CPT-1 activity. Glucose uptake and glucokinase activity were enhanced, whereas glucose production and phosphoenolpyruvate carboxykinase activity were diminished. The increase in the phosphorylation of the insulin receptor, AKT, AMPKα, mTOR, and ERK1/2 conduced to the regulation of hepatic mitochondrial function and energy metabolism. For the first time, the cocoa shell phytochemicals are proved to modulate FGF21 signaling. Results demonstrate the in vitro preventive effect of the phytochemicals from the cocoa shell on NAFLD.

scholarly journals The Radiosensitizing Effect of Zinc Oxide Nanoparticles in Sub-Cytotoxic Dosing Is Associated with Oxidative Stress In Vitro

Materials ◽  
2019 ◽  
Vol 12 (24) ◽  
pp. 4062
Author(s):  
Till Jasper Meyer ◽  
Agmal Scherzad ◽  
Helena Moratin ◽  
Thomas Eckert Gehrke ◽  
Julian Killisperger ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Zinc Oxide ◽  
Zinc Oxide Nanoparticles ◽  
Oxidative Dna Damage ◽  
Clonogenic Survival ◽  
Oxide Nanoparticles ◽  
Radiosensitizing Effect ◽  
Primary Fibroblasts

Radioresistance is an important cause of head and neck cancer therapy failure. Zinc oxide nanoparticles (ZnO-NP) mediate tumor-selective toxic effects. The aim of this study was to evaluate the potential for radiosensitization of ZnO-NP. The dose-dependent cytotoxicity of ZnO-NP20 nm and ZnO-NP100 nm was investigated in FaDu and primary fibroblasts (FB) by an MTT assay. The clonogenic survival assay was used to evaluate the effects of ZnO-NP alone and in combination with irradiation on FB and FaDu. A formamidopyrimidine-DNA glycosylase (FPG)-modified single-cell microgel electrophoresis (comet) assay was applied to detect oxidative DNA damage in FB as a function of ZnO-NP and irradiation exposure. A significantly increased cytotoxicity after FaDu exposure to ZnO-NP20 nm or ZnO-NP100 nm was observed in a concentration of 10 µg/mL or 1 µg/mL respectively in 30 µg/mL of ZnO-NP20 nm or 20 µg/mL of ZnO-NP100 nm in FB. The addition of 1, 5, or 10 µg/mL ZnO-NP20 nm or ZnO-NP100 nm significantly reduced the clonogenic survival of FaDu after irradiation. The sub-cytotoxic dosage of ZnO-NP100 nm increased the oxidative DNA damage compared to the irradiated control. This effect was not significant for ZnO-NP20 nm. ZnO-NP showed radiosensitizing properties in the sub-cytotoxic dosage. At least for the ZnO-NP100 nm, an increased level of oxidative stress is a possible mechanism of the radiosensitizing effect.

scholarly journals Honeybush Extracts (Cyclopia spp.) Rescue Mitochondrial Functions and Bioenergetics against Oxidative Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Anastasia Agapouda ◽  
Veronika Butterweck ◽  
Matthias Hamburger ◽  
Dalene de Beer ◽  
Elizabeth Joubert ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Hot Water ◽  
Human Neuroblastoma ◽  
Atp Production ◽  
Physiological Conditions ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Scientific Attention

Mitochondrial dysfunction plays a major role not only in the pathogenesis of many oxidative stress or age-related diseases such as neurodegenerative as well as mental disorders but also in normal aging. There is evidence that oxidative stress and mitochondrial dysfunction are the most upstream and common events in the pathomechanisms of neurodegeneration. Cyclopia species are endemic South African plants and some have a long tradition of use as herbal tea, known as honeybush tea. Extracts of the tea are gaining more scientific attention due to their phenolic composition. In the present study, we tested not only the in vitro mitochondria-enhancing properties of honeybush extracts under physiological conditions but also their ameliorative properties under oxidative stress situations. Hot water and ethanolic extracts of C. subternata, C. genistoides, and C. longifolia were investigated. Pretreatment of human neuroblastoma SH-SY5Y cells with honeybush extracts, at a concentration range of 0.1-1 ng/ml, had a beneficial effect on bioenergetics as it increased ATP production, respiration, and mitochondrial membrane potential (MMP) after 24 hours under physiological conditions. The aqueous extracts of C. subternata and C. genistoides, in particular, showed a protective effect by rescuing the bioenergetic and mitochondrial deficits under oxidative stress conditions (400 μM H2O2 for 3 hours). These findings indicate that honeybush extracts could constitute candidates for the prevention of oxidative stress with an impact on aging processes and age-related neurodegenerative disorders potentially leading to the development of a condition-specific nutraceutical.

scholarly journals Dual Roles of Helicobacter pylori NapA in Inducing and Combating Oxidative Stress

2006 ◽  
Vol 74 (12) ◽  
pp. 6839-6846 ◽  
Author(s):  
Ge Wang ◽  
Yang Hong ◽  
Adriana Olczak ◽  
Susan E. Maier ◽  
Robert J. Maier
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Wild Type Mouse ◽  
Wild Type ◽  
Oxygen Intermediates ◽  
Physiological Analysis ◽  
H Pylori

ABSTRACT Neutrophil-activating protein (NapA) has been well documented to play roles in human neutrophil recruitment and in stimulating host cell production of reactive oxygen intermediates (ROI). A separate role for NapA in combating oxidative stress within H. pylori was implied by studies of various H. pylori mutant strains. Here, physiological analysis of a napA strain was the approach used to assess the iron-sequestering and stress resistance roles of NapA, its role in preventing oxidative DNA damage, and its importance to mouse colonization. The napA strain was more sensitive to oxidative stress reagents and to oxygen, and it contained fourfold more intracellular free iron and more damaged DNA than the parent strain. Pure, iron-loaded NapA bound to DNA, but native NapA did not, presumably linking iron levels sensed by NapA to DNA damage protection. Despite its in vitro phenotype of sensitivity to oxidative stress, the napA strain showed normal (like that of the wild type) mouse colonization efficiency in the conventional in vivo assay. By use of a modified mouse inoculation protocol whereby nonviable H. pylori is first inoculated into mice, followed by (live) bacterial strain administration, an in vivo role for NapA in colonization efficiency could be demonstrated. NapA is the critical component responsible for inducing host-mediated ROI production, thus inhibiting colonization by the napA strain. An animal colonization experiment with a mixed-strain infection protocol further demonstrated that the napA strain has significantly decreased ability to survive when competing with the wild type. H. pylori NapA has unique and separate roles in gastric pathogenesis.

scholarly journals Transthyretin Maintains Muscle Homeostasis through the Novel Shuttle Pathway of Thyroid Hormones during Myoblast Differentiation

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1565 ◽  
Author(s):  
Eun Ju Lee ◽  
Sibhghatulla Shaikh ◽  
Dukhwan Choi ◽  
Khurshid Ahmad ◽  
Mohammad Hassan Baig ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormones ◽  
Muscle Growth ◽  
Vital Role ◽  
Myoblast Differentiation ◽  
Mouse Muscle ◽  
Total Body Mass ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
Muscle Homeostasis

Skeletal muscle, the largest part of the total body mass, influences energy and protein metabolism as well as maintaining homeostasis. Herein, we demonstrate that during murine muscle satellite cell and myoblast differentiation, transthyretin (TTR) can exocytose via exosomes and enter cells as TTR- thyroxine (T4) complex, which consecutively induces the intracellular triiodothyronine (T3) level, followed by T3 secretion out of the cell through the exosomes. The decrease in T3 with the TTR level in 26-week-old mouse muscle, compared to that in 16-week-old muscle, suggests an association of TTR with old muscle. Subsequent studies, including microarray analysis, demonstrated that T3-regulated genes, such as FNDC5 (Fibronectin type III domain containing 5, irisin) and RXRγ (Retinoid X receptor gamma), are influenced by TTR knockdown, implying that thyroid hormones and TTR coordinate with each other with respect to muscle growth and development. These results suggest that, in addition to utilizing T4, skeletal muscle also distributes generated T3 to other tissues and has a vital role in sensing the intracellular T4 level. Furthermore, the results of TTR function with T4 in differentiation will be highly useful in the strategic development of novel therapeutics related to muscle homeostasis and regeneration.

scholarly journals Theβ-SiC Nanowires (~100 nm) Induce Apoptosis via Oxidative Stress in Mouse Osteoblastic Cell Line MC3T3-E1

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Weili Xie ◽  
Qi Xie ◽  
Meishan Jin ◽  
Xiaoxiao Huang ◽  
Xiaodong Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Dna Damage ◽  
Morphological Changes ◽  
Osteoblastic Cell ◽  
Osteoblastic Cell Line ◽  
Sic Nanowires ◽  
Tissue Replacement ◽  
Transmission Electron ◽  
First Time

Silicon carbide (SiC), a compound of silicon and carbon, with chemical formula SiC, the beta modification (β-SiC), with a zinc blende crystal structure (similar to diamond), is formed at temperature below1700∘C.β-SiC will be the most suitable ceramic material for the future hard tissue replacement, such as bone and tooth. Thein vitrocytotoxicity ofβ-SiC nanowires was investigated for the first time. Our results indicated that 100 nm long SiC nanowires could significantly induce the apoptosis in MC3T3-E1 cells, compared with 100 μm long SiC nanowires. And 100 nm long SiC nanowires increased oxidative stress in MC3T3-E1 cells, as determined by the concentrations of MDA (as a marker of lipid peroxidation) and 8-OHdG (indicator of oxidative DNA damage). Moreover, transmission electron microscopy (TEM) was performed to evaluate the morphological changes of MC3T3-E1 cells. After treatment with 100 nm long SiC nanowires, the mitochondria were swelled and disintegrated, and the production of ATP and the total oxygen uptake were also decreased significantly. Therefore,β-SiC nanowires may have limitations as medical material.

Fibronectin Type III Domain Containing 5 Alleviates the Inflammation and Apoptosis in Lipopolysaccharide- Induced Intestinal Epithelial Cells

2020 ◽  
Vol 10 (5) ◽  
pp. 669-675
Author(s):  
Junzhi Pan ◽  
Jie Zhang
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Intestinal Injury ◽  
Intestinal Epithelial ◽  
Sod Activity ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
Related Proteins ◽  
Fibronectin Type

Intestinal injury caused by sepsis has multiple effects on the pathophysiology and development of sepsis. In this study, we aimed to explore the role of FNDC5 in progression of sepsis-induced intestinal injury. The expression of FNDC5 in blood samples of patients with sepsis-induced intestinal injury and IEC-6 cells was measured by qRT-PCR assay. Cell viability and inflammatory cytokines were evaluated by CCK-8 and ELISA assay, respectively. Oxidative stress level was detected by DCFH-DA staining and corresponding kit. Tunel assay and western blot analysis were performed to assess cell apoptosis. FNDC5 expression in patients with sepsis-induced intestinal injury was significantly decreased. The stimulation of LPS reduced expression level of FNDC5 and inhibited cell growth in IEC-6 cells. Overexpression of FNDC5 suppressed the productions of TNF-a, IL-1 , IL-6 and MCP1, diminished the level of ROS and MPO while enhanced the SOD activity. Additionally, upregulation of FNDC5 ameliorated cell apoptosis and repressed the levels of apoptosis-related proteins. FNDC5 could play a crucial role in the inflammation, oxidative stress and apoptosis in sepsis-induced intestinal injury.

scholarly journals Oxidative stress-mediated mitochondrial dysfunction facilitates mesenchymal stem cell senescence in ankylosing spondylitis

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Guiwen Ye ◽  
Zhongyu Xie ◽  
Huiqiong Zeng ◽  
Peng Wang ◽  
Jinteng Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cell ◽  
Ankylosing Spondylitis ◽  
Mitochondrial Dysfunction ◽  
Chronic Inflammatory Disease ◽  
Atp Production ◽  
Cycle Arrest ◽  
Markers Of Oxidative Stress ◽  
Cellular Dysfunction

Abstract Ankylosing spondylitis (AS) is a chronic inflammatory disease possessing a morbid serum microenvironment with enhanced oxidative stress. Long-term exposure to an oxidative environment usually results in cellular senescence alone with cellular dysfunction. Mesenchymal stem cells (MSCs) are a kind of stem cell possessing strong capabilities for immunoregulation, and senescent MSCs may increase inflammation and participate in AS pathogenesis. The objective of this study was to explore whether and how the oxidative serum environment of AS induces MSC senescence. Here, we found that AS serum facilitated senescence of MSCs in vitro, and articular tissues from AS patients exhibited higher expression levels of the cell cycle arrest-related proteins p53, p21 and p16. Importantly, the levels of advanced oxidative protein products (AOPPs), markers of oxidative stress, were increased in AS serum and positively correlated with the extent of MSC senescence induced by AS serum. Furthermore, MSCs cultured with AS serum showed decreased mitochondrial membrane potential and ATP production together with a reduced oxygen consumption rate. Finally, we discovered that AS serum-induced mitochondrial dysfunction resulted in elevated reactive oxygen species (ROS) in MSCs, and ROS inhibition successfully rescued MSCs from senescence. In conclusion, our data demonstrated that the oxidative serum environment of AS facilitated MSC senescence through inducing mitochondrial dysfunction and excessive ROS production. These results may help elucidate the pathogenesis of AS and provide potential targets for AS treatment.

LncRNA ELFN1-AS1 promotes esophageal cancer progression by up-regulating GFPT1 via sponging miR-183-3p

2020 ◽  
Vol 401 (9) ◽  
pp. 1053-1061 ◽  
Author(s):  
Chunyan Zhang ◽  
Hongkai Lian ◽  
Linsen Xie ◽  
Ningwei Yin ◽  
Yuanbo Cui
Keyword(s):  
Esophageal Cancer ◽  
Cancer Progression ◽  
Critical Role ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Over Expression ◽  
Fibronectin Type Iii ◽  
Cancer Genome Atlas ◽  
Fibronectin Type Iii Domain

AbstractAccumulating studies highlight the critical role of long non-coding RNAs (lncRNAs) in the development of various human cancers. Extracellular leucine rich repeat and fibronectin type III domain containing 1-antisense RNA 1 (ELFN1-AS1) was shown to be a newly found lncRNA that abnormally expressed in human tumors. However, till now the specific function of this lncRNA in esophageal cancer (ESCA) remains unknown. In this study, we discovered that higher ELFN1-AS1 expression indicated shorter patient survival in pan-cancer, including ESCA, using online The Cancer Genome Atlas (TCGA) tools. The lncRNA ELFN1-AS1 was significantly up-regulated in ESCA tissues and cell lines when compared with the counterparts. Down-regulation of ELFN1-AS1 restrained cell proliferation, migration, and invasion of ESCA in vitro. In addition, we found that the expression of microRNA-183-3p (miR-183-3p) and ELFN1-AS1 or glutamine-fructose-6-phosphate transaminase 1 (GFPT1) were inversely correlated in ESCA. Both ELFN1-AS1 and GFPT1 are direct targets of miR-183-3p in ESCA. The effects of ELFN1-AS1 knockdown on ESCA progression were partially rescued by inhibition of miR-183-3p or over-expression of GFPT1. In summary, the results of this study suggest that the lncRNA ELFN1-AS1 facilitates the progression of ESCA by acting as a competing endogenous RNA (ceRNA) to promote GFPT1 expression via sponging miR-183-3p.

scholarly journals Role of Irisin in Myocardial Infarction, Heart Failure, and Cardiac Hypertrophy

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2103
Author(s):  
Ming-Yun Ho ◽  
Chao-Yung Wang
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Endothelial Damage ◽  
Acid Oxidation ◽  
Fibronectin Type Iii ◽  
Metabolic Imbalance ◽  
Failure Prognosis ◽  
Fibronectin Type Iii Domain

Irisin is a myokine derived from the cleavage of fibronectin type III domain-containing 5. Irisin regulates mitochondrial energy, glucose metabolism, fatty acid oxidation, and fat browning. Skeletal muscle and cardiomyocytes produce irisin and affect various cardiovascular functions. In the early phase of acute myocardial infarction, an increasing irisin level can reduce endothelial damage by inhibiting inflammation and oxidative stress. By contrast, higher levels of irisin in the later phase of myocardial infarction are associated with more cardiovascular events. During different stages of heart failure, irisin has various influences on mitochondrial dysfunction, oxidative stress, metabolic imbalance, energy expenditure, and heart failure prognosis. Irisin affects blood pressure and controls hypertension through modulating vasodilatation. Moreover, irisin can enhance vasoconstriction via the hypothalamus. Because of these dual effects of irisin on cardiovascular physiology, irisin can be a critical therapeutic target in cardiovascular diseases. This review focuses on the complex functions of irisin in myocardial ischemia, heart failure, and cardiac hypertrophy.

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