scholarly journals Resistance exercise affects catheter-related thrombosis in rats through miR-92a-3p, oxidative stress and the MAPK/NF-κB pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Cui Wen ◽  
Yanping Ying ◽  
Huihan Zhao ◽  
Qingjuan Jiang ◽  
Xiao Gan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Resistance Exercise ◽  
Exercise Intervention ◽  
Mitogen Activated Protein Kinase ◽  
Expression Level ◽  
Ros Production ◽  
Stress Injury ◽  
Expression Levels ◽  
The Right ◽  
Catheter Related Thrombosis

Abstract Background MiR-92a-3p and oxidative stress are associated with catheter-related thrombosis (CRT). As a kind of physical intervention, resistance exercise can effectively promote blood circulation. In this study, we investigated the roles of miR-92a-3p, oxidative stress and the P38 mitogen-activated protein kinase/nuclear factor-κB (MAPK/NF-κB) pathway in CRT during resistance exercise. Methods The rat CRT model was used for resistance exercise intervention. Moreover, pathological changes from the right jugular vein to the right auricle were observed under an electron microscope. In addition, reactive oxygen species (ROS) production, malondialdehyde (MDA) activity and heme oxygenase (HO-1) level in rat serum were detected via ELISA. The expression levels of miR-92A-3p and HO-1 in the vascular tissues of the rats were determined via real-time quantitative PCR. Additionally, the expression levels of HO-1, NF-κB P65, p38MAPK and IκBa in the venous tissues of the rats were analysed by Western blot analysis. Results The pathological results showed that the thrombosis incidence rate in the CRT + RE group was lower than that in the CRT group. In the CRT group, the expression levels of ROS and MDA, which are markers related to oxidative stress in serum, significantly increased whilst the expression of HO-1 decreased. In the venous tissue, the expression of miR-92a-3p increased, the level of HO-1 decreased, the levels of p38MAPK and NF-κB p65 significantly increased but that of P-IκBa and IκBa significantly decreased. In the CRT + RE group, after administering the resistance exercise intervention, ROS production and MDA activity in serum significantly decreased, the expression level of HO-1 increased and the expression level of miR-92a-3p in the venous tissues significantly decreased and was negatively correlated with that of HO-1. The levels of p38MAPK and NF-κB p65 significantly decreased but that of P- IκBa and IκBa significantly increased. Conclusion Resistance exercise intervention downregulated miR-92a-3p expression, repaired oxidative stress injury and prevented CRT formation.

scholarly journals Effects of miR-92a-3P, Oxidative Stress, and the MAPK/NF-κB Pathway on Catheter-Related Thrombosis Prevention After Resistance Exercise

2021 ◽  
Author(s):  
Cui Wen ◽  
Yanping Ying ◽  
Huihan Zhao ◽  
Qingjuan Jiang ◽  
Xiao Gan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Resistance Exercise ◽  
Exercise Intervention ◽  
Mitogen Activated Protein Kinase ◽  
Expression Level ◽  
Ros Production ◽  
Stress Injury ◽  
Expression Levels ◽  
Vascular Tissues ◽  
The Right

Abstract Background: MiR-92a-3p and oxidative stress are associated with catheter-related thrombosis (CRT). As a kind of physical intervention, resistance exercise can effectively promote blood circulation. In this study, we investigated the roles of miR-92a-3p, oxidative stress, and the P38 mitogen-activated protein kinase/nuclear factor-κB (MAPK/NF-κB) pathway on CRT during resistance exercise. Methods: The rat CRT model was used for resistance exercise intervention. Moreover, pathological changes from the right jugular vein to the right auricle were observed under an electron microscope. In addition, reactive oxygen species (ROS) production, malondialdehyde (MDA) activity, and heme oxygenase (HO-1) level in rat serum were detected via ELISA. Furthermore, expression levels of miR-92A-3p and HO-1 in the vascular tissues of the rats were detected via real-time quantitative PCR. Additionally, expression levels of HO-1, NF-κB P65, p38MAPK, and IκBa in the venous tissues of the rats were analyzed by Western blot analysis. Results: Thrombosis incidence rate in CRT+RE group was lower than that in CRT group. In the thrombosis model, markers related to oxidative stress and miR-92a-3p increased. After administering the resistance exercise intervention, ROS production and MDA activity significantly decreased, the expression level of HO-1 increased, and the expression level of miR-92A-3p in the vascular tissues significantly decreased. The levels of p38MAPK and NF-κB p65 significantly decreased but that of IκBa significantly increased. Conclusion: Resistance exercise intervention downregulated miR-92a-3p expression, repaired oxidative stress injury, and prevented CRT formation.

scholarly journals Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) increases Nrf2 expression via miR-27a mediation to prevent memory dysfunction in diabetic rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shiva Ebrahimpour ◽  
Seyedeh Bahar Shahidi ◽  
Mahnoosh Abbasi ◽  
Zahra Tavakoli ◽  
Abolghasem Esmaeili
Keyword(s):  
Oxidative Stress ◽  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Superparamagnetic Iron Oxide ◽  
Diabetic Rats ◽  
Expression Level ◽  
Oxide Nanoparticles ◽  
Antioxidant Genes ◽  
Expression Levels ◽  
Nrf2 Expression

Abstract Oxidative stress is one of the earliest defects involved in the development of diabetes-induced cognitive impairment. Nrf2 is the master regulator of the cellular antioxidant system can be regulated by some microRNAs. The study aimed to evaluate the effects of quercetin (QC) and quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on Nrf2-controlled antioxidant genes through the redox-sensitive miR-27a. Expression levels of miR-27a, Nrf2, SOD1, GPX1, and CAT were measured by quantitative real-time PCR. Moreover, the oxidative stress parameters including total antioxidant capacity (TAC) and histological alterations were investigated. The expression level of miR-27a was significantly up-regulated in diabetic rats. While expression levels of Nrf2, SOD1, GPX1, and CAT were significantly down-regulated under diabetic condition. Interestingly, QCSPIONs decreased expression level of miR-27a and subsequently enhanced the expression levels of Nrf2, SOD1, and CAT to the control level. No significant difference was observed in the expression level of GPX1. Besides, QC in pure and especially conjugated form was able to normalize TAC and regenerate pathological lesions in STZ-diabetic rats. Our result demonstrates that QCSPIONs as an effective combined therapy can decrease miR-27a expression, which in turn increases the Nrf2 expression and responsive antioxidant genes, resulting in improvement of memory dysfunction in diabetic rats.

scholarly journals Cabbage (Brassica oleracea var. capitata) Protects against H2O2-Induced Oxidative Stress by Preventing Mitochondrial Dysfunction in H9c2 Cardiomyoblasts

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Dong Kwon Yang
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mitogen Activated Protein Kinase ◽  
Ros Production ◽  
Hepatic Diseases ◽  
Mitochondrial Functions ◽  
Wide Range ◽  
H9c2 Cardiomyoblasts ◽  
Cabbage Extract

Oxidative stress plays an important role in the progression of cardiac diseases, including ischemia/reperfusion injury, myocardial infarction, and heart failure. Growing evidence indicates that cabbage has various pharmacological properties against a wide range of diseases, such as cardiovascular diseases, hepatic diseases, and cancer. However, little is known about its effects on oxidative stress in cardiomyocytes or the underlying mechanisms. Therefore, the present study examined the effects of cabbage extract on oxidative stress in H9c2 cardiomyoblasts. Cell viability, reactive oxygen species (ROS) production, apoptosis, mitochondrial functions, and expression levels of mitogen-activated protein kinase (MAPK) proteins were analyzed to elucidate the antioxidant effects of this extract. Cabbage extract protected against H2O2-induced cell death and did not elicit any cytotoxic effects. In addition, cabbage extract suppressed ROS production and increased expression of antioxidant proteins (SOD-1, catalase, and GPx). Cabbage extract also inhibited apoptotic responses and activation of MAPK proteins (ERK1/2, JNK, and p-38) in oxidative stress-exposed H9c2 cells. Notably, cabbage extract preserved mitochondrial functions upon oxidative stress. These findings reveal that cabbage extract protects against oxidative stress and suggest that it can be used as an alternative therapeutic strategy to prevent the oxidative stress in the heart.

scholarly journals Protective Effects of Tianxiangdan Capsule Drug-Containing Plasma Against H2O2-Induced Oxidative Stress in Primary Cardiomyocytes

2021 ◽  
Author(s):  
Mei Tang ◽  
Lin Jiang ◽  
Gaerma Dugujia ◽  
Yuche Wu ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Cell Apoptosis ◽  
Cell Damage ◽  
Network Pharmacology ◽  
Protective Effects ◽  
Active Components ◽  
Stress Injury ◽  
Expression Levels ◽  
Intracellular Ca

Abstract Background: Tianxiangdan capsule (TXD), developed in our hospital, has been clinically used in the treatment of coronary heart disease angina pectoris. This study aimed at evaluating the mechanisms of TXD against myocardial ischemia and to provide evidence for its subsequent clinical application. METHODS: Active components and mechanisms of action of TXD against myocardial ischemia were predicted and analyzed by network pharmacology and molecular docking. The oxidative damage model was established using H2O2, which caused myocardial cell damage. The MTT assay was used to evaluate cell viability, Hoechst33342 staining, while cleaved caspase-3 immunofluorescence staining was used to determine cell apoptosis. Fluorescent probe method detected ROS and intracellular Ca2+, while spectrophotometry was used to measure SOD, MDA, and NO levels in myocardial cells. Western blotting was used to detect the expression levels of ESR1, PI3K, AKT, and eNOS in cells. RESULTS: It was found that TXD plays a protective role in myocardial ischemia through the estrogen pathway, and its main active components were isoflavones. The TXD drug-containing plasma exhibited increased cell survival rates and suppressed MDA levels, elevated SOD and NO levels, and significantly suppressed ROS levels as well as intracellular Ca2+ levels. Moreover, the TXD drug-containing plasma pretreated cells had significantly suppressed PI3K and AKT expression levels, as well as elevated ESR1 and eNOS expression levels. Conclusion: TXD may exhibit estrogen-like effects, through the estrogen pathway enhances cardiomyocytes' antioxidant capacities, and improves oxidative stress injury as well as cell apoptosis.

Effect of β-D-Mannuronic Acid (M2000) on Oxidative Stress Enzymes’ Gene Using Healthy Donor Peripheral Blood Mononuclear Cells for Evaluating the Anti-Aging Property

2019 ◽  
Vol 16 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Mahsa Taeb ◽  
Abdollah Jafarzadeh ◽  
Seyed Shahabeddin Mortazavi-Jahromi ◽  
Nahid Zainodini ◽  
Mohammad Reza Mirzaei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Expression Level ◽  
High Dose ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Blood Mononuclear Cells

Objective: This research aimed to study the anti-aging and anti-inflammatory effects of low and high doses of the β-D-mannuronic (M2000) on gene expression of enzymes involved in oxidative stress (including SOD2, GST, GPX1, CAT, iNOS, and MPO) in peripheral blood mononuclear cells (PBMCs) of healthy donors under in vitro conditions. Methods: The PBMCs were separated and the RNAs were then extracted and the cDNAs synthesized, and expression levels of the mentioned genes were detected by qRT-PCR. Results: Our results indicated that the high dose of this drug could significantly reduce the expression level of the SOD2 gene compared to the lipopolysaccharide (LPS) group (p < 0.0001). Moreover, it was found that the high dose of this drug could significantly decrease the expression level of the GST gene compared to the LPS group (p < 0.0001). However, no significant reductions were observed in expression levels of the CAT and GPX1 genes compared to the LPS group. Furthermore, our data revealed that the level of iNOS and MPO gene expression was significantly reduced, in both doses of M2000, respectively, compared to the LPS group (p < 0.0001). Conclusion: This research showed that M2000 as a novel NSAID with immunosuppressive properties could modify oxidative stress through lowering expression levels of the SOD2, GST, iNOS, and MPO genes compared to the healthy expression levels, with a probable reduction of the risk of developing inflammatory diseases related to age and aging.

Abstract 25: Polyphenolic - Ellagic Acid Suppresses Mitophagy- Induced Necrotic Cell Death During Doxorubicin Cardiotoxicity

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Rimpy Dhingra ◽  
Abhinav Dhingra ◽  
Rahul Jayas ◽  
Lorrie A. Kirshenbaum
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cardiac Myocytes ◽  
Ellagic Acid ◽  
Necrotic Cell Death ◽  
Ros Production ◽  
Necrotic Cell ◽  
Dual Emission ◽  
Stress Injury ◽  
Oxidative Stress Injury

Reactive oxygen species (ROS) play a major role in cardiac dysfunction during myocardial ischemia. ROS production has been linked to oxidative stress injury and mitochondrial perturbations including permeability transition pore opening (mPTP), loss of mitochondrial membrane potential ([[Unable to Display Character: &#8710;]]Ψm) and necrotic cell death. Previously we identified the inducible Bcl-2 protein, Bnip3 as critical regulator of mitochondrial function and cell death of ventricular myocytes. Polyphenolic compounds including ellagic acid from pomegranate, have strong anti-oxidant properties. The effects of ellagic acid on oxidative stress injury in the heart has not been explored. In this report, we provide new compelling evidence that ellagic acid suppressed mitochondrial ROS production, loss of [[Unable to Display Character: &#8710;]]Ψm and necrotic cell death of cardiac myocytes induced by doxorubicin (DOX) or hypoxia. We further show mechanistically that the cytoprotective effects of ellagic acid were related to the transcriptional repression of Bnip3. In contrast to vehicle treated cells, cells treated with DOX or hypoxia displayed a marked increase in Bnip3 expression and mitochondrial association, concordant with increased ROS, mPTP, and loss of [[Unable to Display Character: &#8710;]]Ψm. Consistent with these mitochondrial defects there was a marked increase in mitophagy as confirmed by the dual emission Mitokeima probe that detects autophagic degradation by labelling mitochondria containing autophagosomes fused with lysosome. Mitophagy was accompanied by a marked increase in LDH release, loss of nuclear HMGB1 immunostaining and cell death. Interestingly, cells treated with ellagic acid were resistant to mitochondrial and the cytotoxic effects of DOX displaying reduced ROS production, mitophagy and were indistinguishable from vehicle treated control cells with respect to cell viability. Notably, Dox-induced Bnip3 expression was dramatically reduced in cells treated with ellagic acid. Hence, the findings of the present study demonstrate that ellagic acid suppresses mitochondrial perturbations and cell death of cardiac myocytes by mechanism that links to the repression of mitochondrial Bnip3.

scholarly journals A mitochondria-targeted antioxidant and a thyroid hormone affect carotenoid ketolase gene expression and bill redness in zebra finches

2020 ◽  
Author(s):  
Alejandro Cantarero ◽  
Pedro Andrade ◽  
Miguel Carneiro ◽  
Adrián Moreno-Borrallo ◽  
Carlos Alonso-Alvarez
Keyword(s):  
Thyroid Hormone ◽  
Expression Level ◽  
Ros Production ◽  
Zebra Finches ◽  
Quality Indices ◽  
Inner Mitochondrial Membrane ◽  
Compensatory Mechanisms ◽  
Carotenoid Concentration ◽  
Expression Levels ◽  
Trade Offs

ABSTRACTConspicuous ornaments in animals can evolve to reveal individual quality when their production/maintenance costs make them reliable as signals or if their expression level is intrinsically linked to quality by some unfalsifiable mechanism (quality indices). The latter has been mostly associated with traits constrained by body size. However, red ketocarotenoid-based coloured ornaments may also have evolved as quality indices because their production could be closely linked to individual metabolism and, particularly, to the cell respiration at the inner mitochondrial membrane (IMM). This mechanism would supposedly not depend on resource (yellow carotenoids) availability, thus discarding allocation trade-offs. A gene coding for a ketolase enzyme (CYP2J19) responsible for converting dietary yellow carotenoids to red ketocarotenoids has recently been described in birds. It is not known, however, if this ketolase is involved in mitochondrial metabolism and if its expression level and activity is resource independent. Here, we manipulated the metabolism of captive male zebra finches by an antioxidant designed to penetrate the IMM (mitoTEMPO) and a thyroid hormone (triiodothyronine; T3) with known hypermetabolic effects. The expression levels of a ketocarotenoid-based ornament (bill redness) and CYP2J19 were measured. MitoTEMPO downregulated CYP2J19 expression, supporting the mitochondrial involvement in ketolase function. T3 also reduced CYP2J19 expression, but at an intermediate dosage, this effect being buffered by mitoTEMPO. Bill redness seemed to show a similar interacting effect. Nevertheless, this faded when CYP2J19 expression level was controlled for as a covariate. We argue that the well-known mitoTEMPO effect in reducing mitochondrial reactive oxygen species (ROS) production (particularly superoxide) could have interfered on redox signalling mechanisms controlling ketolase transcription. High T3 levels, contrarily, can lead to high ROS production but also trigger compensatory mechanisms, which may explain the U-shaped effect with dosage on CYP2J19 expression levels. Bill CYP2J19 expression values were also positively correlated to redness and circulating substrate carotenoid levels. Nonetheless, treatment effects did not change when controlling for blood carotenoid concentration, suggesting that resource-availability dependence was irrelevant. Finally, our findings reveal a role for thyroid hormones in the expression of carotenoid-based ornaments that has virtually been ignored until now.

Effect of Donepezil on Vascular Dementia in Rats via PI3K/AKT Pathway

2022 ◽  
Vol 12 (5) ◽  
pp. 1046-1052
Author(s):  
Jianmin Zhang ◽  
Qianwen Zhu ◽  
Xingnan Wang ◽  
Jian Wang
Keyword(s):  
Oxidative Stress ◽  
Vascular Dementia ◽  
Learning And Memory ◽  
Brain Tissue ◽  
Caspase 3 ◽  
Akt Pathway ◽  
Ros Production ◽  
Sod Activity ◽  
Ht22 Cells ◽  
Stress Injury

Background: Previous studies have shown that Donepezil has therapeutic effects on vascular dementia (VD). PI3K/AKT involves in oxidative stress injury and cell apoptosis. This study investigated whether Donepezil affects the neurological function and apoptosis of VD mice via PI3K/AKT signaling. Methods: Mice were assigned into Sham group, VD group, VD+Donepezil groupfollowed by analysis of mice learning and memory ability by Water maze test, p-AKT expression by Western blot, Caspase-3 activity, MDA content, SOD activity and GSH-Px in hippocampus. HT22 cells were cultured and separated into control group, I-R group and I-R+Donepezil group followed by measuring p-AKT level, ROS content and apoptosis. Results: Learning and memory abilities of VD group mice were significantly decreased, Caspase-3 activity and MDA in brain tissue were significantly increased, along with decreased SOD activity, GSH-Px and p-AKT level. Donepezil treatment can significantly improve VD mice learning and memory ability, reduce Caspase-3 activity and MDA in brain tissue, increase SOD activity, GSH-Px and p-AKT level. In vitro, I-R treatment significantly induced apoptosis of HT22 cells, increased ROS production and decreased p-AKT level. Donepezil treatment could up-regulate p-AKT in HT22 cells and reduce apoptosis and ROS production in HT22 cells. Conclusion: Donepezil improves the function of brain nerve in VD mice through regulating PI3K/AKT pathway, thus reducing oxidative stress injury and apoptosis of brain nerve cells.

Abstract 424: Loss of Sirt2 Protects Against Pressure Overload- and Ischemic Reperfusion Injury-induced Cardiac Dysfunction

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Teruki Sato ◽  
Xiaoyan Yan ◽  
Hsiang-Chun Chang ◽  
Chen Chunlei ◽  
Jason S Shapiro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Reperfusion Injury ◽  
Cardiac Dysfunction ◽  
Pressure Overload ◽  
Cardiac Response ◽  
Neonatal Rat ◽  
Ros Production ◽  
Wild Type ◽  
Stress Injury

Introduction: Sirtuins are NAD+ dependent deacetylases and critical regulators of energy metabolism and response to oxidative stress. Sirtuin2 (SIRT2) is a cytoplasmic member of the sirtuin family, and has been shown to regulate cellular iron homeostasis through deacetylation of nuclear factor erythroid-derived 2-related factor 2 (NRF2). However, whether SIRT2-NRF2 pathway is involved in the development of heart failure remains unknown. Methods and results: To investigate the functional role of SIRT2 in the response to cardiac stress, SIRT2 knockout (KO) mice and their littermate controls were subjected to pressure overload by transverse aortic constriction (TAC). SIRT2 KO had normal appearance and cardiovascular parameters at baseline. However, in response to TAC, Sirt2 -/- mice displayed resistance to the pathological hypertrophic response, whereas wild type (WT) mice developed cardiac hypertrophy and heart failure. In addition, SIRT2 KO mice displayed less cardiac damage after /reperfusion injury. SIRT2 knockdown in neonatal rat cardiomyocytes (NRCM) reduced reactive oxygen species (ROS) production and cell death after H2O2 treatment. Since cellular oxidative stress is one of major contributor of cardiac dysfunction caused by both I/R injury and pressure overload, we examined whether NRF2 is associated with SIRT2-mediated cardiac response to oxidative stress. Levels of NRF2 was upregulated in NRCM with SIRT2 knockdown and treated with H2O2 compared to wild type (WT) cells. Moreover, NRF2 is translocated into the nucleus and its anti-oxidant target proteins are upregulated in NRCM with SIRT2 knockdown. SIRT2 was also found to bind and deacetylate NRF2 directly as determined by co-immunoprecipitation studies. This led to a reduction of its nuclear translocation and transcriptional activity. Finally, knockdown of both SIRT2 and NRF2 diminished the effects of SIRT2 knockdown on ROS production and cellular damage. Conclusion: These results indicate that SIRT2 contributes to pressure overload and I/R injury induced heart impairment in mice, and promotes oxidative stress injury in cardiomyocytes via deacetylating NRF2 and altering its activity.

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