scholarly journals TXNIP Links Innate Host Defense Mechanisms to Oxidative Stress and Inflammation in Retinal Muller Glia under Chronic Hyperglycemia: Implications for Diabetic Retinopathy

2012 ◽  
Vol 2012 ◽  
pp. 1-19 ◽  
Author(s):  
Takhellambam S. Devi ◽  
Icksoo Lee ◽  
Maik Hüttemann ◽  
Ashok Kumar ◽  
Kwaku D. Nantwi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Er Stress ◽  
Host Defense ◽  
Defense Mechanisms ◽  
Immune Response Gene ◽  
Ros Generation ◽  
Muller Glia ◽  
Müller Glia ◽  
Cellular Defense

Thioredoxin Interacting Protein (TXNIP) mediates retinal inflammation, gliosis, and apoptosis in experimental diabetes. Here, we investigate the temporal response of Muller glia to high glucose (HG) and TXNIP expression using a rat Muller cell line (rMC1) in culture. We examined if HG-induced TXNIP expression evokes host defense mechanisms in rMC1 in response to metabolic abnormalities. HG causes sustained up-regulation of TXNIP (2 h to 5 days), ROS generation, ATP depletion, ER stress, and inflammation. Various cellular defense mechanisms are activated by HG: (i) NLRP3 inflammasome, (ii) ER stress response (sXBP1), (iii) hypoxic-like HIF-1αinduction, (iv) autophagy/mitophagy, and (v) apoptosis. We also foundin vivothat streptozocin-induced diabetic rats have higher retinal TXNIP and innate immune response gene expression than normal rats. Knock down of TXNIP by intravitreal siRNA reduces inflammation (IL-1β) and gliosis (GFAP) in the diabetic retina. TXNIP ablationin vitroprevents ROS generation, restores ATP level and autophagic LC3B induction in rMC1. Thus, our results show that HG sustains TXNIP up-regulation in Muller glia and evokes a program of cellular defense/survival mechanisms that ultimately lead to oxidative stress, ER stress/inflammation, autophagy and apoptosis. TXNIP is a potential target to ameliorate blinding ocular complications of diabetic retinopathy.

PERK mediates oxidative stress and adipogenesis in Graves’ orbitopathy pathogenesis

2021 ◽  
Author(s):  
JaeSang Ko ◽  
Ji-Young Kim ◽  
Min Kyung Chae ◽  
Eun Jig Lee ◽  
Jin Sook Yoon
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Er Stress ◽  
Adipogenic Differentiation ◽  
Ros Generation ◽  
Mrna Levels ◽  
Graves Orbitopathy ◽  
Orbital Fibroblasts

We examined endoplasmic reticulum (ER) stress-related gene expression in orbital tissues from patients with Graves’ orbitopathy (GO) and the effects of silencing protein kinase RNA-like endoplasmic reticulum kinase (PERK) in primary orbital fibroblast cultures to demonstrate the therapeutic potential of PERK-modulating agents in GO management. The expression of ER stress related genes in orbital tissue harvested from individuals with or without GO was studied using real-time polymerase chain reaction. The role of PERK in GO pathogenesis was examined through small-interfering RNA (siRNA)-mediated silencing in cultured primary orbital fibroblasts. Intracellular reactive oxygen species (ROS) levels induced in response to cigarette smoke extract (CSE) or hydrogen peroxide were measured using 5-(and 6)-carboxy-20,70-dichlorodihydrofluorescein diacetate staining and flow cytometry. Cells were stained with Oil Red O, and adipogenesis-related transcription factor expression was evaluated through western blotting after adipogenic differentiation. PERK, activating transcription factor 4 (ATF4), and CCAAT-enhancer-binding protein (C/EBP)-homologous protein(CHOP)mRNA levels were significantly higher in GO orbital tissues than in non-GO orbital tissues. PERK silencing inhibited CSE- or hydrogen peroxide-induced ROS generation. After adipogenic differentiation, GO orbital fibroblasts revealed decreased lipid droplets and downregulation of C/EBPα, C/EBPβ, and peroxisome proliferator-activator gamma (PPARγ) in PERK siRNA-transfected cells. The orbital tissues of patients with GO were exposed to chronic ER stress and subsequently exhibited enhanced unfolded protein response (especially through the PERK pathway). PERK silencing reduced oxidative stress and adipogenesis in GO orbital fibroblasts in vitro. Our results imply that PERK-modulating agents can potentially be used to manage GO.

The role of corneal crystallins in the cellular defense mechanisms against oxidative stress

2008 ◽  
Vol 19 (2) ◽  
pp. 100-112 ◽  
Author(s):  
Natalie Lassen ◽  
William J. Black ◽  
Tia Estey ◽  
Vasilis Vasiliou
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Cellular Defense

scholarly journals Antioxidants: Pharmacothearapeutic Boon for Diabetes

2021 ◽  
Author(s):  
Varuna Suresh ◽  
Amala Reddy ◽  
Pavithra Muthukumar ◽  
Thendarl Selvam
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Cellular Response ◽  
Cell Function ◽  
Glucose Variability ◽  
Diabetic Rats ◽  
Long Term Effects ◽  
Free Radical Damage ◽  
Cellular Defense ◽  
Elevated Glucose

Glucose-induced oxidative stress can be found related to “glucose variability” and “glucose memory”. The irregular low and elevated glucose conditions cause damage to endothelial cell function than a steady, constant rise in level of glucose. Activation of PKC, NADPH oxidases, and mitochondrial oxidants are some of the pathways exhibited as a result of this aggravated cellular response. Regarding glucose memory, long after the normalization elevated level of glucose in the endothelial cells of diabetic rats and culture, a existance or ‘memory’ of induced basement membrane mRNA is expressed. This demonstrates that glucose causes dangerous long-term effects beyond the hyperglycemia period. Oxidative stress give rise to glucotoxicity and lipotoxicity which are phenomena’s related to diabetes. Following the pathogenesis of diabetes, hyperglycemia and hyperlipidemia exerts a supplementary toxic effect on the beta-cells. So, hyperglycemia can be considered as a requirement for the destructive effects of lipotoxicity. Thus glucolipotoxicity can be considered as a substitute for lipotoxicity which relates the detrimental correlation between lipids and beta-cell function. Generally, the antioxidant pharmacotherapy can be coupled with drugs to boost the natural cellular defense mechanisms as the naturally existing antioxidant components, which neutralizes free radical damage. This considers antioxidant a boon tool for pharmacotherapeutic agent.

scholarly journals Oxidative Stress and Calcium Dyshomeostasis Mediated CPF-Induces EPC Cell Apoptosis and Necroptosis

2021 ◽  
Author(s):  
Zhiying Miao ◽  
Jiawen Cui ◽  
Meijin Yu ◽  
Xiaohua Teng
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Aquatic Organisms ◽  
Ros Generation ◽  
Organophosphate Insecticide ◽  
Epithelioma Papulosum Cyprini ◽  
Apoptotic Pathway ◽  
The Common ◽  
Stress Related Genes ◽  
Novel Concept

Abstract Chlorpyrifos (CPF) is a broadly used organophosphate insecticide, and as environmental contamination has been confirmed to be harmful to the health of humans and animals, the effects of CPF on fish are still unclear. We aim to detect whether CPF has effects on the common carps, and identify the mechanisms of the effects. In accordance with the IC50 of CPF for epithelioma papulosum cyprini (EPC) cells was 8.945 µM, 0, 3, 5 and 7 µM CPF were marked as C, L, M and H group. The results indicated that CPF exposure led to oxidative stress in EPC cells. Moreover, Calcium ion (Ca2+) imaging indicated that CPF triggers Ca2+ dyshomeostasis, as induced ER Ca2+ fluxed into cytoplasm and mitochondrial, and mediates endoplasmic reticulum (ER) stress and mitochondrial Ca2+ overload, which have further confirmed with the increased transcription of ER stress related genes. Meanwhile, CPF induced collapse of mitochondrial membrane potential (MMP), enhancement of ROS generation and depletion of ATP level in both cytoplasm and mitochondrial, substantiated mitochondrial dysfunction has been evoked. Besides, the AO/EB staining and flow cytometry analysis ascertained that CPF induces apoptosis and necroptosis in EPC cells. Hence, we further verified that via determining the expression of apoptotic pathway genes and necroptotic pathway genes. Consequently, we illuminated the mechanisms of CPF effects on the common carps from the perspective of Ca2+ homeostasis, and provided a novel concept for investigating the toxicity of CPF as environmental pollution on aquatic organisms.

scholarly journals Increased Oxidative Stress as a Selective Anticancer Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jiahui Liu ◽  
Zhichong Wang
Keyword(s):  
Oxidative Stress ◽  
Cancer Cells ◽  
Defense Mechanisms ◽  
Redox Regulation ◽  
Ros Generation ◽  
Normal Cells ◽  
Hypoxic Environment ◽  
Intracellular Ros ◽  
Anticancer Treatment

Reactive oxygen species (ROS) are closely related to tumorgenesis. Under hypoxic environment, increased levels of ROS induce the expression of hypoxia inducible factors (HIFs) in cancer stem cells (CSCs), resulting in the promotion of the upregulation of CSC markers, and the reduction of intracellular ROS level, thus facilitating CSCs survival and proliferation. Although the ROS level is regulated by powerful antioxidant defense mechanisms in cancer cells, it is observed to remain higher than that in normal cells. Cancer cells may be more sensitive than normal cells to the accumulation of ROS; consequently, it is supposed that increased oxidative stress by exogenous ROS generation therapy has an effect on selectively killing cancer cells without affecting normal cells. This paper reviews the mechanisms of redox regulation in CSCs and the pivotal role of ROS in anticancer treatment.

scholarly journals Tocotrienol-Rich Fraction Ameliorates Antioxidant Defense Mechanisms and Improves Replicative Senescence-Associated Oxidative Stress in Human Myoblasts

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Shy Cian Khor ◽  
Wan Zurinah Wan Ngah ◽  
Yasmin Anum Mohd Yusof ◽  
Norwahidah Abdul Karim ◽  
Suzana Makpol
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Glutathione Peroxidase ◽  
Defense Mechanisms ◽  
Antioxidant Defense ◽  
Replicative Senescence ◽  
Ros Generation ◽  
Tocotrienol Rich Fraction

During aging, oxidative stress affects the normal function of satellite cells, with consequent regeneration defects that lead to sarcopenia. This study aimed to evaluate tocotrienol-rich fraction (TRF) modulation in reestablishing the oxidative status of myoblasts during replicative senescence and to compare the effects of TRF with other antioxidants (α-tocopherol (ATF) andN-acetyl-cysteine (NAC)). Primary human myoblasts were cultured to young, presenescent, and senescent phases. The cells were treated with antioxidants for 24 h, followed by the assessment of free radical generation, lipid peroxidation, antioxidant enzyme mRNA expression and activities, and the ratio of reduced to oxidized glutathione. Our data showed that replicative senescence increased reactive oxygen species (ROS) generation and lipid peroxidation in myoblasts. Treatment with TRF significantly diminished ROS production and decreased lipid peroxidation in senescent myoblasts. Moreover, the gene expression of superoxide dismutase(SOD2), catalase(CAT),and glutathione peroxidase(GPX1)was modulated by TRF treatment, with increased activity of superoxide dismutase and catalase and reduced glutathione peroxidase in senescent myoblasts. In comparison to ATF and NAC, TRF was more efficient in heightening the antioxidant capacity and reducing free radical insults. These results suggested that TRF is able to ameliorate antioxidant defense mechanisms and improves replicative senescence-associated oxidative stress in myoblasts.

scholarly journals Phenolic Extract from Aralia nudicaulis L. Rhizomes Inhibits Cellular Oxidative Stresses

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4458
Author(s):  
Quentin Lion ◽  
Andre Pichette ◽  
Mouadh Mihoub ◽  
Vakhtang Mshvildadze ◽  
Jean Legault
Keyword(s):  
Oxidative Stress ◽  
Phenolic Compounds ◽  
Defense Mechanisms ◽  
Ros Generation ◽  
Protective Effects ◽  
Growing Period ◽  
Oxidative Stresses ◽  
Biological Potential ◽  
Anti Inflammatory ◽  
Dermal Cells

UV-B and IR-A radiation are important inducers of biological changes in skin involving ROS generation. The overloading of antioxidant defense mechanisms by ROS production could lead to photoaging and photocarcinogenesis processes. Various traditional usages are reported for Aralia nudicaulis L. extracts, including treatment of dermatological disorders. Antioxidant and anti-inflammatory properties have already been reported for other Aralia species possibly due to the presence of phenolic compounds. However, the phenolic composition and the potential activity of A. nudicaulis rhizomes extract against oxidative stress and UV/IR damages have not been investigated. The main aims of this study were to prepare a fraction enriched in phenolic compounds (FEPC) from A. nudicaulis rhizomes, to identify its major phenolic compounds and to assess its potential for protective effects against oxidative stress induced by UV-B, IR-A or inflammation. A quantitative LC-MS study of FEPC shows that chlorogenic, caffeic and protocatechuic acids are the main phenolic compounds present, with concentrations of 15.6%, 15.3% and 4.8% of the total composition, respectively. With a validated analytical method, those compounds were quantified over different stages of the growing period. As for biological potential, first this extract demonstrates antioxidant and anti-inflammatory activities. Furthermore, ROS generation induced by IR-A and UV-B were strongly inhibited by A. nudicaulis extract, suggesting that Aralia nudicaulis L. rhizome extract could protect dermal cells against oxidative stress induced by UV-B and IR-A.

scholarly journals Cardiac Oxidative Stress and the Therapeutic Approaches to the Intake of Antioxidant Supplements and Physical Activity

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3483
Author(s):  
Kosar Valaei ◽  
Shima Taherkhani ◽  
Hamid Arazi ◽  
Katsuhiko Suzuki
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Antioxidant Defense ◽  
Ischemia Reperfusion ◽  
Creatine Supplementation ◽  
Critical Factor ◽  
Ros Generation ◽  
Omega 3 ◽  
Antioxidant Supplements ◽  
Experimental Treatments

Reactive oxygen species (ROS) are strongly reactive chemical entities that include oxygen regulated by enzymatic and non-enzymatic antioxidant defense mechanisms. ROS contribute significantly to cell homeostasis in the heart by regulating cell proliferation, differentiation, and excitation-contraction coupling. When ROS generation surpasses the ability of the antioxidant defense mechanisms to buffer them, oxidative stress develops, resulting in cellular and molecular disorders and eventually in heart failure. Oxidative stress is a critical factor in developing hypoxia- and ischemia-reperfusion-related cardiovascular disorders. This article aimed to discuss the role of oxidative stress in the pathophysiology of cardiac diseases such as hypertension and endothelial dysfunction. This review focuses on the various clinical events and oxidative stress associated with cardiovascular pathophysiology, highlighting the benefits of new experimental treatments such as creatine supplementation, omega-3 fatty acids, microRNAs, and antioxidant supplements in addition to physical exercise

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