MiR-22-3p Suppresses Vascular Remodeling and Oxidative Stress by Targeting CHD9 during the Development of Hypertension

2021 ◽  
pp. 1-11
Author(s):  
Hanqing Chen ◽  
Xiru Xu ◽  
Zhengqing Liu ◽  
Yong Wu
Keyword(s):  
Oxidative Stress ◽  
Vascular Remodeling ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Spontaneously Hypertensive ◽  
Aortic Smooth Muscle ◽  
Phenotype Switch ◽  
And Oxidative Stress

Hypertension is considered a risk factor for a series of systematic diseases. Known factors including genetic predisposition, age, and diet habits are strongly associated with the initiation of hypertension. The current study aimed to investigate the role of miR-22-3p in hypertension. In this study, we discovered that the miR-22-3p level was significantly decreased in the thoracic aortic vascular tissues and aortic smooth muscle cells (ASMCs) of spontaneously hypertensive rats. Functionally, the overexpression of miR-22-3p facilitated the switch of ASMCs from the synthetic to contractile phenotype. To investigate the underlying mechanism, we predicted 11 potential target mRNAs for miR-22-3p. After screening, chromodomain helicase DNA-binding 9 (CHD9) was validated to bind with miR-22-3p. Rescue assays showed that the co-overexpression of miR-22-3p and CHD9 reversed the inhibitory effect of miR-22-3p mimics on cell proliferation, migration, and oxidative stress in ASMCs. Finally, miR-22-3p suppressed vascular remodeling and oxidative stress in vivo. Overall, miR-22-3p regulated ASMC phenotype switch by targeting CHD9. This new discovery provides a potential insight into hypertension treatment.

scholarly journals In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells

2020 ◽  
Vol 9 (6) ◽  
pp. 734-740
Author(s):  
Yigit Sezer ◽  
Ayse Tarbin Jannuzzi ◽  
Marilyn A Huestis ◽  
Buket Alpertunga
Keyword(s):  
Oxidative Stress ◽  
Neuronal Cells ◽  
Underlying Mechanism ◽  
Synthetic Cannabinoid ◽  
Stress Effects ◽  
Legal High ◽  
New Generation ◽  
And Oxidative Stress

Abstract Background: JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as “spice,” “herbal incense,” or “herbal blend,” as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug’s toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. Methods: SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150 μM JWH-018 over 24 h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. Results: JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P < 0.05. Discussion/Conclusion: JWH-018 produced oxidative stress in SH-SY5Y cells that could be an underlying mechanism of JWH-018 neurotoxicity. Additional in vivo animal and human-based studies are needed to confirm our findings.

scholarly journals Cyanamide Phytotoxicity in Soybean (Glycine max) Seedlings involves Aldehyde Dehydrogenase Inhibition and Oxidative Stress

2015 ◽  
Vol 10 (5) ◽  
pp. 1934578X1501000
Author(s):  
John S. Maninang ◽  
Shin Okazaki ◽  
Yoshiharu Fujii
Keyword(s):  
Oxidative Stress ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Knock Out ◽  
Soybean Seedlings ◽  
Semialdehyde Dehydrogenase ◽  
Phytotoxic Effect ◽  
And Oxidative Stress

The phytotoxic effect of the allelochemical cyanamide has been well-documented yet the underlying mechanism for this phenomenon has not been fully characterized. Cognizant of the putative inhibitory effect of cyanamide on aldehyde dehydrogenases (ALDHs), we hereby show that the capacity of mitochondrial preparations from cyanamide-treated soybean seedlings to oxidize acetaldehyde and succinic-semialdehyde was dose-dependently reduced to at most 55% and 70%, respectively. Cyanamide-treated plants exhibited oxidative stress (i.e. increased lipid peroxidation and H2O2 accumulation) that was exacerbated upon exposure to UV-A – symptoms reminiscent of ALDH and succinic-semialdehyde dehydrogenase (SSADH) knock-out Arabidopsis mutants. We suggest that the inhibition of mitochondrial ALDH and SSADH may be a contributory mechanism to the burst in oxidative stress mediated by cyanamide.

Potential Role of Dual NF-κB and Oxidative Stress Pathway Inhibitor, OT-304 as a Novel Drug Resistance-Reversing Agent.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4211-4211
Author(s):  
Shaker A. Mousa ◽  
Ghanshyam Patil ◽  
Abdelhadi Rebbaa
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Tumor Cells ◽  
Genetic Alterations ◽  
Potential Candidate ◽  
Drug Resistant ◽  
P Glycoprotein ◽  
And Oxidative Stress

Abstract The development of resistance to chemotherapy represents an adaptive biological response by tumor cells that leads to treatment failure and patient relapse. During the course of their evolution (intrinsic resistance) or in response to chemotherapy (acquired resistance), tumor cells may undergo genetic alterations to possess a drug resistant phenotype. Dysregulation of membrane transport proteins and cellular enzymes, as well as altered susceptibility to commit to apoptosis are among the mechanisms that contribute to the genesis of acquired drug resistance. Recently, the development of approaches to prevent and/or to reverse this phenomenon has attracted special interest and a number of drug candidates have been identified. Despite strong effects observed for these candidates in vitro, however, most of them fail in vivo. In the present study, we have identified a novel small molecule inhibitor of dual NF-κB and oxidative stress pathways, OT-304, as a potential candidate to reverse drug resistance. Initial investigations indicate that this compound effectively inhibits proliferation of doxorubicin-sensitive and doxorubicin-resistant cells to the same extent, suggesting that it is capable of bypassing the development of drug resistance. Additional experiments reveal that OT-304 enhances cancer cell sensitivity to doxorubicin and to etoposide, particularly in cells characterized by the over-expression of the drug transporter P-glycoprotein. These findings suggest that either the expression/and or the function of P-glycoprotein could be affected by OT-304. In vivo studies using tumor xenografts in nude mice showed that OT-304 is also capable of preventing the growth of drug resistant cancer cells. This later finding further confirms the role of OT-304 as a drug resistance-reversing agent and warrants further pre-clinical and clinical investigation to determine its efficacy in treating aggressive tumors.

scholarly journals The Role of the Nrf2 Signaling in Obesity and Insulin Resistance

2020 ◽  
Vol 21 (18) ◽  
pp. 6973 ◽  
Author(s):  
Shiri Li ◽  
Natsuki Eguchi ◽  
Hien Lau ◽  
Hirohito Ichii
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Leucine Zipper ◽  
Close Association ◽  
Underlying Mechanism ◽  
Related Factor ◽  
Basic Leucine Zipper ◽  
State Of Research ◽  
And Oxidative Stress

Obesity, a metabolic disorder characterized by excessive accumulation of adipose tissue, has globally become an increasingly prevalent disease. Extensive studies have been conducted to elucidate the underlying mechanism of the development of obesity. In particular, the close association of inflammation and oxidative stress with obesity has become increasingly evident. Obesity has been shown to exhibit augmented levels of circulating proinflammatory cytokines, which have been associated with the activation of pathways linked with inflammation-induced insulin resistance, a major pathological component of obesity and several other metabolic disorders. Oxidative stress, in addition to its role in stimulating adipose differentiation, which directly triggers obesity, is considered to feed into this pathway, further aggravating insulin resistance. Nuclear factor E2 related factor 2 (Nrf2) is a basic leucine zipper transcription factor that is activated in response to inflammation and oxidative stress, and responds by increasing antioxidant transcription levels. Therefore, Nrf2 has emerged as a critical new target for combating insulin resistance and subsequently, obesity. However, the effects of Nrf2 on insulin resistance and obesity are controversial. This review focuses on the current state of research on the interplay of inflammation and oxidative stress in obesity, the role of the Nrf2 pathway in obesity and insulin resistance, and the potential use of Nrf2 activators for the treatment of insulin resistance.

scholarly journals Apple Can Act as Anti-Aging on Yeast Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Vanessa Palermo ◽  
Fulvio Mattivi ◽  
Romano Silvestri ◽  
Giuseppe La Regina ◽  
Claudio Falcone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ascorbic Acid ◽  
Free Radicals ◽  
Cardiovascular Diseases ◽  
Yeast Cells ◽  
Eukaryotic Organism ◽  
Biochemical Studies ◽  
And Oxidative Stress

In recent years, epidemiological and biochemical studies have shown that eating apples is associated with reduction of occurrence of cancer, degenerative, and cardiovascular diseases. This association is often attributed to the presence of antioxidants such as ascorbic acid (vitamin C) and polyphenols. The substances that hinder the presence of free radicals are also able to protect cells from aging. In our laboratory we used yeast, a unicellular eukaryotic organism, to determinein vivoefficacy of entire apples and their components, such as flesh, skin and polyphenolic fraction, to influence aging and oxidative stress. Our results indicate that all the apple components increase lifespan, with the best result given by the whole fruit, indicating a cooperative role of all apple components.

scholarly journals Irisin alleviates obesity-related spermatogenesis dysfunction via the regulation of the AMPKα signalling pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang Mu ◽  
Huang-Guan Dai ◽  
Ling-Bo Luo ◽  
Jing Yang
Keyword(s):  
Oxidative Stress ◽  
Sperm Count ◽  
Underlying Mechanism ◽  
Signalling Pathway ◽  
Protective Effects ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase

Abstract Background Infertility is a common complication in obese men. Oxidative stress and testicular apoptosis play critical roles in obesity-induced spermatogenesis dysfunction. It has been reported that irisin, an exercise-induced myokine, may attenuate oxidative damage and testicular apoptosis in several diseases; however, its role in obesity-induced spermatogenesis dysfunction remains unclear. The purpose of this study was to investigate the role and underlying mechanism of irisin in obesity-induced dysfunction of spermatogenesis. Methods Male mice were fed a high-fat diet (HFD) for 24 weeks to establish a model of obesity-induced spermatogenesis dysfunction. To explore the effects of irisin, mice were subcutaneously infused with recombinant irisin for 8 weeks beginning at 16 weeks after starting a HFD. To confirm the role of AMP-activated protein kinase α (AMPKα), AMPKα-deficient mice were used. Results The data showed decreased serum irisin levels in obese patients, which was negatively correlated with sperm count and progressive motility. Irisin was downregulated in the plasma and testes of obese mice. Supplementation with irisin protected against HFD-induced spermatogenesis dysfunction and increased testosterone levels in mice. HFD-induced oxidative stress, endoplasmic reticulum (ER) stress and testicular apoptosis were largely attenuated by irisin treatment. Mechanistically, we identified that irisin activated the AMPKα signalling pathway. With AMPKα depletion, we found that the protective effects of irisin on spermatogenesis dysfunction were abolished in vivo and in vitro. Conclusions In conclusion, we found that irisin alleviated obesity-related spermatogenesis dysfunction via activation of the AMPKα signalling pathway. Based on these findings, we hypothesized that irisin is a potential therapeutic agent against obesity-related spermatogenesis dysfunction.

scholarly journals OsnR is an autoregulatory negative transcription factor controlling redox-dependent stress responses in Corynebacterium glutamicum

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Haeri Jeong ◽  
Younhee Kim ◽  
Heung-Shick Lee
Keyword(s):  
Oxidative Stress ◽  
Corynebacterium Glutamicum ◽  
Stress Responses ◽  
Promoter Region ◽  
Underlying Mechanism ◽  
In Vitro Assays ◽  
Expression Of Genes

Abstract Background Corynebacterium glutamicum is used in the industrial production of amino acids and nucleotides. During the course of fermentation, C. glutamicum cells face various stresses and employ multiple regulatory genes to cope with the oxidative stress. The osnR gene plays a negative regulatory role in redox-dependent oxidative-stress responses, but the underlying mechanism is not known yet. Results Overexpression of the osnR gene in C. glutamicum affected the expression of genes involved in the mycothiol metabolism. ChIP-seq analysis revealed that OsnR binds to the promoter region of multiple genes, including osnR and cg0026, which seems to function in the membrane-associated redox metabolism. Studies on the role of the osnR gene involving in vitro assays employing purified OsnR proteins and in vivo physiological analyses have identified that OsnR inhibits the transcription of its own gene. Further, oxidant diamide stimulates OsnR-binding to the promoter region of the osnR gene. The genes affected by the overexpression of osnR have been found to be under the control of σH. In the osnR-overexpressing strain, the transcription of sigH is significantly decreased and the stimulation of sigH transcription by external stress is lost, suggesting that osnR and sigH form an intimate regulatory network. Conclusions Our study suggests that OsnR not only functions as a transcriptional repressor of its own gene and of those involved in redox-dependent stress responses but also participates in the global transcriptional regulation by controlling the transcription of other master regulators, such as sigH.

Role of Syzygium cumini seed extract in the chemoprevention of in vivo genomic damage and oxidative stress

2011 ◽  
Vol 134 (2) ◽  
pp. 329-333 ◽  
Author(s):  
Renganathan Arun ◽  
M. Velayutham Dass Prakash ◽  
Suresh K. Abraham ◽  
Kumpati Premkumar
Keyword(s):  
Oxidative Stress ◽  
Seed Extract ◽  
Syzygium Cumini ◽  
Genomic Damage ◽  
And Oxidative Stress

scholarly journals Berries and oxidative stress markers: an overview of human intervention studies

2015 ◽  
Vol 6 (9) ◽  
pp. 2890-2917 ◽  
Author(s):  
Cristian Del Bo’ ◽  
Daniela Martini ◽  
Marisa Porrini ◽  
Dorothy Klimis-Zacas ◽  
Patrizia Riso
Keyword(s):  
Oxidative Stress ◽  
Intervention Studies ◽  
Human Intervention ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Intervention Trials ◽  
And Oxidative Stress

Severalin vitroandin vivostudies have demonstrated that polyphenol-rich berries may counteract oxidative stress. In this review, we summarized the main finding from human intervention trials on the role of berries in the modulation of markers of oxidative lipid, protein and DNA damage.

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