scholarly journals Transcriptome Analysis of Porcine Granulosa Cells in Healthy and Atretic Follicles: Role of Steroidogenesis and Oxidative Stress

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 22
Author(s):  
Li Meng ◽  
Zhenfang Wu ◽  
Kun Zhao ◽  
Jian Tao ◽  
Tam Chit ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Granulosa Cells ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Glutathione Metabolism ◽  
Follicular Atresia ◽  
Rna Seq ◽  
Antioxidant Genes ◽  
Porcine Granulosa Cells ◽  
Apoptotic Factors

One of the main causes of female infertility is a deregulated antral follicular atresia, a process of which the underlying molecular mechanisms are largely unknown. Our objective was therefore to characterize the complex transcriptome changes in porcine granulosa cells of healthy antral (HA) and advanced antral atretic (AA) follicles, using ELISA and RNA-Seq followed by qRT-PCR and immunohistochemistry. Granulosa cell RNA-Seq data revealed 2160 differentially expressed genes, 1483 with higher and 677 with lower mRNA concentrations in AA follicles. Bioinformatic analysis showed that the upregulated genes in AA follicles were highly enriched in inflammation and apoptosis processes, while the downregulated transcripts were mainly highlighted in the steroid biosynthesis pathway and response to oxidative stress processes including antioxidant genes (e.g., GSTA1, GCLC, GCLM, IDH1, GPX8) involved in the glutathione metabolism pathway and other redox-related genes (e.g., RRM2B, NDUFS4). These observations were confirmed by RT-qPCR and immunohistochemistry. Additionally, the granulosa cells of AA follicles express significantly stronger 8-OHdG immunostaining, a marker of oxidative DNA damage, implicating that oxidative stress may participate in follicular atresia. We hypothesize that the decrease in anti-apoptotic factors and steroid hormones coincides with increased oxidative stress markers and the expression of pro-apoptotic factors, all contributing to antral follicular atresia.

scholarly journals Metabolic Profiling Analysis Reveals the Potential Contribution of Barley Sprouts against Oxidative Stress and Related Liver Cell Damage in Habitual Alcohol Drinkers

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 459
Author(s):  
Hyerin Park ◽  
Eunok Lee ◽  
Yunsoo Kim ◽  
Hye Yoon Jung ◽  
Kwang-Min Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Molecular Mechanisms ◽  
Learning Algorithm ◽  
Controlled Trial ◽  
Liver Fat ◽  
Glutathione Metabolism ◽  
Ros Generation ◽  
Potential Contribution ◽  
Glutamyl Transferase

Chronic excessive alcohol consumption is associated with multiple liver defects, such as steatosis and cirrhosis, mainly attributable to excessive reactive oxygen species (ROS) production. Barley sprouts (Hordeum vulgare L.) contain high levels of polyphenols that may serve as potential antioxidants. This study aimed to investigate whether barley sprouts extract powder (BSE) relieves alcohol-induced oxidative stress and related hepatic damages in habitual alcohol drinkers with fatty liver. In a 12-week randomized controlled trial with two arms (placebo or 480 mg/day BSE; n = 76), we measured clinical markers and metabolites at the baseline and endpoint to understand the complex molecular mechanisms. BSE supplementation reduced the magnitude of ROS generation and lipid peroxidation and improved the glutathione antioxidant system. Subsequent metabolomic analysis identified alterations in glutathione metabolism, amino acid metabolism, and fatty acid synthesis pathways, confirming the role of BSE in glutathione-related lipid metabolism. Finally, the unsupervised machine learning algorithm indicated that subjects with lower glutathione reductase at the baseline were responders for liver fat content, and those with higher fatigue and lipid oxidation were responders for γ-glutamyl transferase. These findings suggest that BSE administration may protect against hepatic injury by reducing oxidative stress and changing the metabolism in habitual alcohol drinkers with fatty liver.

scholarly journals Oxidative Stress in Dairy Cows: Insights into the Mechanistic Mode of Actions and Mitigating Strategies

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1918
Author(s):  
Aurele Gnetegha Ayemele ◽  
Mekonnen Tilahun ◽  
Sun Lingling ◽  
Samy Abdelaziz Elsaadawy ◽  
Zitai Guo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Volatile Fatty Acids ◽  
Molecular Mechanisms ◽  
Body Condition Score ◽  
Animal Health ◽  
Protein Carbonyl ◽  
Feed Additives ◽  
High Density Lipoproteins ◽  
Immune Functions ◽  
Antioxidant Genes

This review examines several molecular mechanisms underpinning oxidative stress in ruminants and their effects on blood and milk oxidative traits. We also investigate strategies to alleviate or repair oxidative damages by improving animal immune functions using novel feed additives. Microbial pathogenic cells, feeding management, and body condition score were some of the studied factors, inducing oxidative stress in ruminants. The predominance of Streptococcus spp. (24.22%), Acinetobacter spp. (21.37%), Romboutsia spp. (4.99%), Turicibacter spp., (2.64%), Stenotrophomonas spp. (2.33%), and Enterococcus spp. (1.86%) was found in the microbiome of mastitis cows with a decrease of d-mannose and increase of xanthine:guanine ratio when Streptococcus increased. Diversity of energy sources favoring the growth of Fusobacterium make it a keystone taxon contributing to metritis. Ruminal volatile fatty acids rose with high-concentrate diets that decreased the ruminal pH, causing a lysis of rumen microbes and release of endotoxins. Moreover, lipopolysaccharide (LPS) concentration, malondialdehyde (MDA), and superoxide dismutase (SOD) activities increased in high concentrate cows accompanied by a reduction of total antioxidant capacity (T-AOC), glutathione peroxidase (GPx), and catalase (CAT) activity. In addition, albumin and paraoxonase concentrations were inversely related to oxidative stress and contributed to the protection of low-density and high-density lipoproteins against lipid peroxidation, protein carbonyl, and lactoperoxidase. High concentrate diets increased the expression of MAPK pro-inflammatory genes and decreased the expression of antioxidant genes and proteins in mammary epithelial tissues. The expression levels of NrF2, NQO1, MT1E, UGT1A1, MGST3, and MT1A were downregulated, whereas NF-kB was upregulated with a high-grain or high concentrate diet. Amino-acids, vitamins, trace elements, and plant extracts have shown promising results through enhancing immune functions and repairing damaged cells exposed to oxidative stress. Further studies comparing the long-term effect of synthetic feed additives and natural plant additives on animal health and physiology remain to be investigated.

scholarly journals Endogenous and Exogenous Modulation of Nrf2 Mediated Oxidative Stress Response in Bovine Granulosa Cells: Potential Implication for Ovarian Function

2019 ◽  
Vol 20 (7) ◽  
pp. 1635 ◽  
Author(s):  
Omar Khadrawy ◽  
Samuel Gebremedhn ◽  
Dessie Salilew-Wondim ◽  
Mohamed Taqi ◽  
Christiane Neuhoff ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant System ◽  
Granulosa Cells ◽  
Cellular Proliferation ◽  
Ovarian Function ◽  
Defense Mechanism ◽  
Protective Role ◽  
Mitochondrial Activity ◽  
Antioxidant Genes ◽  
Potential Implication

Nrf2 is a redox sensitive transcription factor regulating the expression of antioxidant genes as defense mechanism against various stressors. The aim of this study is to investigate the potential role of noncoding miRNAs as endogenous and quercetin as exogenous regulators of Nrf2 pathway in bovine granulosa cells. For this cultured granulosa cells were used for modulation of miRNAs (miR-28, 153 and miR-708) targeting the bovine Nrf2 and supplementation of quercentin to investigate the regulatory mechanisms of the Nrf2 antioxidant system. Moreover, cultured cells were treated with hydrogen peroxide to induce oxidative stress in those cells. Our results showed that, oxidative stress activated the expression of Nrf2 as a defense mechanism, while suppressing the expression of those miRNAs. Overexpression of those miRNAs resulted in downregulation of Nrf2 expression resulted in higher ROS accumulation, reduced mitochondrial activity and cellular proliferation. Quercetin supplementation showed its protective role against oxidative stress induced by H2O2 by inducing the expression of antioxidant enzymes. In conclusion, this study highlighted the involvement of miR-153, miR-28 and miR-708 in regulatory network of Nrf2 mediated antioxidant system in bovine granulosa cells function. Furthermore, quercetin at a low dose played a protective role in bovine granulosa cells against oxidative stress damage.

scholarly journals The Neuroprotective Effects ofRatanasampilon Oxidative Stress-Mediated Neuronal Damage in Human Neuronal SH-SY5Y Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Aiqin Zhu ◽  
Zhou Wu ◽  
Jie Meng ◽  
Patrick L. McGeer ◽  
Yi Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Mitogen Activated Protein Kinase ◽  
Tibetan Medicine ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Human Neuroblastoma ◽  
Traditional Tibetan Medicine

We previously found thatRatanasampil(RNSP), a traditional Tibetan medicine, improves the cognitive function of mild-to-moderate AD patients living at high altitude, as well as learning and memory in an AD mouse model (Tg2576); however, mechanism underlying the effects of RNSP is unknown. In the present study, we investigated the effects and molecular mechanisms of RNSP on oxidative stress-induced neuronal toxicity using human neuroblastoma SH-SY5Y cells. Pretreatment with RNSP significantly ameliorated the hydrogen peroxide- (H2O2-) induced cytotoxicity of SH-SY5Y cells in a dose-dependent manner (up to 60 μg/mL). Furthermore, RNSP significantly reduced the H2O2-induced upregulation of 8-oxo-2′-deoxyguanosine (8-oxo-dG, the oxidative DNA damage marker) but significantly reversed the expression of repressor element-1 silencing transcription factor (REST) from H2O2associated (100 μM) downregulation. Moreover, RNSP significantly attenuated the H2O2-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK 1/2) in SH-SY5Y cells. These observations strongly suggest that RNSP may protect the oxidative stress-induced neuronal damage that occurs through the properties of various antioxidants and inhibit the activation of MAPKs. We thus provide the principle molecular mechanisms of the effects of RNSP and indicate its role in the prevention and clinical management of AD.

scholarly journals Chlorella Vulgaris Biomass Supplementation Increased the Abundance of Hepatic Antioxidant Proteins in Relation to Oxidative Stress Reduction in Rabbits

2020 ◽  
Author(s):  
Akeem Babatunde Sikiru ◽  
Arangasamy Arunachalam ◽  
Stephen Sunday Acheneje Egena ◽  
Sejian Veerasamy ◽  
Ippala Janardhan Reddy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chlorella Vulgaris ◽  
Molecular Mechanisms ◽  
Profile Analysis ◽  
Control Group ◽  
Antioxidant Enzyme Activities ◽  
Control Groups ◽  
Antioxidant Genes ◽  
Significant Difference ◽  
Antioxidant Proteins

Abstract Background Chlorella vulgaris is a unicellular microalga that is rich in antioxidant, its supplementation has been reported to reduce oxidative stress via upregulations of antioxidant genes. However, there are scarce reports on its effect on antioxidant protein expressions in rabbits – a situation which necessitate an untargeted proteomic profile analysis due to its supplementation. This is because untargeted proteomics profiling is an approach suitable for assessing the effectiveness of genes code translation into polypeptide chains folded into functional proteins used for specific sub-cellular or extracellular physiological activities. It remains one of the comparative avenues for evaluating the efficacies of drugs and nutraceutical agents including antioxidants. In this study, the antioxidant efficacy of a microalga Chlorella vulgaris was evaluated at molecular levels using its hepatic protein expression in rabbit models. Results After 120 days of the microalga supplementation, protein was extracted from liver of the rabbits for untargeted proteomics profiling using LC-MS/Orbitrap Fusion Tribrid™ peptides quantifier and sequencer. There were five-hundred and eleven (511) proteins identified; and among the proteins, 191 were specific to the control group while 186 were specific to the Treatment group; and 134 were common to both groups. Independent samples t-test of the protein abundance indicated that there was a significant difference (p = 0.01) between the treatment and the control groups. There was also a significant reduction in the malondialdehyde concentrations (p = 0.01), higher total antioxidant capacities (p = 0.002), and increased antioxidant enzyme activities (p = 0.05) between the treatment and control groups.Conclusion The study concluded that one of the molecular mechanisms associated with Chlorella vulgaris intake reduction of the hepatic oxidative stress is increased abundances of antioxidant proteins and reduction of the lipid peroxidation and these led to a suggestion that the microalga is a potent antioxidant agent suitable for protecting against oxidative stress in rabbits and other domestic food producing animals.

scholarly journals Genome-wide mRNA profiling identifies the NRF2-regulated lymphocyte oxidative stress status in patients with silicosis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yingzheng Zhao ◽  
Guangcui Xu ◽  
Haibin Li ◽  
Meiyu Chang ◽  
Cheng Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress State ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Set Enrichment Analysis ◽  
Receptor Interaction ◽  
Related Factor ◽  
Healthy Controls ◽  
Rna Seq ◽  
Antioxidant Genes

Abstract Background The immunomodulatory abnormalities of silicosis are related to the lymphocyte oxidative stress state. The potential effect of antioxidant therapy on silicosis may depend on the variation in nuclear factor erythroid 2-related factor 2 (NRF2)-regulated antioxidant genes in peripheral blood mononuclear cells (PBMCs). As NRF2 is a redox-sensitive transcription factor, its possible roles and underlying mechanism in the treatment of silicosis need to be clarified. Methods Ninety-two male patients with silicosis and 87 male healthy volunteers were randomly selected. PBMCs were isolated from fresh blood from patients with silicosis and healthy controls. The lymphocyte oxidative stress state was investigated by evaluating NRF2 expression and NRF2-dependent antioxidative genes in PBMCs from patients with silicosis. Key differentially expressed genes (DEGs) and signaling pathways were identified utilizing RNA sequencing (RNA-Seq) and bioinformatics technology. Gene set enrichment analysis was used to identify the differences in NRF2 signaling networks between patients with silicosis and healthy controls. Results The number of monocytes was significantly higher in patients with silicosis than that of healthy controls. Furthermore, RNA-Seq findings were confirmed using quantitative polymerase chain reaction and revealed that NRF2-regulated DEGs were associated with glutathione metabolism, transforming growth factor-β, and the extracellular matrix receptor interaction signaling pathway in PBMCs from patients with silicosis. The top 10 hub genes were identified by PPI analysis: SMAD2, MAPK3, THBS1, SMAD3, ITGB3, integrin alpha-V (ITGAV), von Willebrand factor (VWF), BMP4, CD44, and SMAD7. Conclusions These findings suggest that NRF2 signaling regulates the lymphocyte oxidative stress state and may contribute to fibrogenic responses in human PBMCs. Therefore, NRF2 might serve as a novel preventive and therapeutic candidate for silicosis.

scholarly journals MON-027 Activation of Endoplasmic Reticulum Stress Mediates Oxidative Stress-Induced Apoptosis of Granulosa Cells in Ovaries Affected by Endometrioma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Chisato Kunitomi ◽  
Miyuki Harada ◽  
Jerilee Mariam Khong Azahry
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Granulosa Cells ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Ovarian Dysfunction ◽  
High Oxidative Stress ◽  
Induced Apoptosis ◽  
Sensor Proteins ◽  
Apoptotic Factors

Abstract Endometriosis exerts detrimental effects on ovarian physiology and compromises follicular health. Granulosa cells of endometriosis patients are characterized by increased apoptosis, as well as high oxidative stress. Among several pathophysiologic factors associated with endometriosis, it is expected that oxidative stress contributes to the induction of apoptosis in granulosa cells, although the underlying mechanism remains unclear. Endoplasmic reticulum (ER) stress, a local factor closely associated with oxidative stress, has emerged as a critical regulator of ovarian function. We hypothesized that ER stress is activated by high oxidative stress in granulosa cells in ovaries with endometrioma and mediates oxidative stress-induced apoptosis. Ovaries from patients with endometrioma and control were collected to determine apoptosis, oxidative stress and ER stress by TUNEL, immunohistochemical staining of 8-OHdG and ER stress sensors, respectively. Human granulosa-lutein cells (GLCs) obtained from IVF patients were cultured with H2O2 (an oxidative stress inducer) or tauroursodeoxycholic acid (TUDCA, an ER stress inhibitor in clinical use) to assess apoptosis and ER stress by quantitative PCR and FACS. Activity of pro-apoptotic factors was determined by caspase-8 activity assay and western blotting for cleaved caspase-3. Human GLCs from patients with endometrioma expressed up to two times higher level of mRNAs associated with the unfolded protein response (UPR), including ATF4, ATF6, the spliced form of XBP1, HSPA5, and CHOP. In addition, the levels of phosphorylated ER stress sensor proteins, IRE1 and PERK, were elevated. Given that ER stress results in phosphorylation of ER stress sensor proteins and induces UPR factors, these findings indicate that these cells were under ER stress. H2O2 increased expression of UPR-associated mRNAs in cultured human GLCs, and this effect was abrogated by pre-treatment with TUDCA. Treatment with H2O2 increased apoptosis and the activity of pro-apoptotic factors caspase-8 and caspase-3, both of which were attenuated by TUDCA. Our findings suggest that activated ER stress induced by high oxidative stress in granulosa cells in ovaries with endometrioma mediates apoptosis of these cells, leading to ovarian dysfunction in endometriosis patients. Targeting ER stress with currently clinically available ER stress inhibitors, or with these agents in combination with antioxidants, may serve as a novel strategy for rescuing endometriosis-associated ovarian dysfunction.

Idarubicin-induced oxidative stress and apoptosis in cardiomyocytes: An in vitro molecular approach

2021 ◽  
pp. 096032712110337
Author(s):  
Yang Zhang ◽  
Qi Li ◽  
Dongsheng Xu ◽  
Tengteng Li ◽  
Zehui Gu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Network Analysis ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Tunel Assay ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Qrt Pcr ◽  
Caspase Family ◽  
Apoptotic Factors

Idarubicin (IDA) is an anthracycline antibiotic, frequently used for the treatment of various human cancers. In vivo rodent model studies have identified a variety of possible adverse outcomes from IDA including heart effects like increased heart weights, myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. Despite significant investigations, the molecular mechanisms responsible for the cardiotoxicity of IDA have not been fully clarified. The aim of the current study was to investigate the effects of IDA on the HL-1 cardiac muscle cell. Different concentrations of IDA (10−6, 10−5, 10−4, and 10−3 M) were used at different time (6, 12, 24, and 48 h) periods, and the Cell Counting Kit-8 (CCK-8); 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) probe method; and enzyme-linked immunosorbent assay (ELISA) were used to detect the oxidative stress level. In addition, we used network analysis to predict IDA-induced cardiotoxicity. The TUNEL assay, qRT-PCR, ELISA assay, and Western blotting detection of related apoptotic factors including caspase family, Bax, and Bcl-2. Overall, we found that IDA was generally more toxic at high concentrations or extended durations of exposure. At the same time, IDA can increase the content of reactive oxygen species (ROS), malondialdehyde (MDA), and decrease the level of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in cells, and increase the content of lactate dehydrogenase (LDH) and nitric oxide synthase (NOS) in the medium. Network analysis showed that the apoptosis signaling pathway was activated; specifically, the caspase family was involved in the signal pathway. The results of the TUNEL assay, qRT-PCR, ELISA, and Western blot found that IDA can activate apoptotic factors. The mechanism may be related to the activation of apoptosis signaling pathway. These results indicate that the cardiotoxic effects of IDA are most likely associated with oxidative stress and ROS formation, which finally ends in apoptotic factors’ activation and induction of cell apoptosis.

Genome-Wide mRNA Profiling Identifies  the NRF2- Regulated Lymphocyte Oxidative Status in Patients with Silicosis

2021 ◽  
Author(s):  
yingzheng zhao ◽  
Guangcui Xu ◽  
Haibin Li ◽  
Meiyu Chang ◽  
Cheng Xiong ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Set Enrichment Analysis ◽  
Receptor Interaction ◽  
Glutathione Metabolism ◽  
Related Factor ◽  
Rna Seq ◽  
Antioxidant Genes ◽  
Oxidative State

Abstract BackgroundThe immunomodulatory abnormalities of silicosis are related to the lymphocyte oxidative state. The potential effect of antioxidant therapy on silicosis may depend on the variation in nuclear factor erythroid 2-related factor 2 (NRF2)-regulated antioxidant genes in peripheral blood mononuclear cells (PBMCs). As NRF2 is a redox-sensitive transcription factor, its possible roles and underlying mechanism in the treatment of silicosis need to be clarified.MethodsIn this study, the lymphocyte oxidative state was investigated by evaluating NRF2 expression and NRF2-dependent antioxidative genes in PBMCs from patients with silicosis. Key differentially expressed genes (DEGs) and signaling pathways were identified utilizing RNA sequencing (RNA-Seq) and bioinformatics technology. Gene set enrichment analysis was used to identify the differences in NRF2 signaling networks between patients with silicosis and healthy controls.ResultsThe number of monocytes increased significantly through cytology detection in patients with silicosis. Furthermore, RNA-Seq findings were confirmed using quantitative polymerase chain reaction and revealed that NRF2-regulated DEGs were associated with glutathione metabolism, transforming growth factor-β, and the extracellular matrix receptor interaction signaling pathway in PBMCs from patients with silicosis. The top 10 hub genes were identified by PPI analysis: SMAD2, MAPK3, THBS1, SMAD3, ITGB3, integrin alpha-V (ITGAV), von Willebrand factor (VWF), BMP4, CD44, and SMAD7.ConclusionsThese findings suggest that NRF2 signaling regulates the lymphocyte oxidative state and may contribute to fibrogenic responses in human PBMCs. Therefore, NRF2 might serve as a novel preventive and therapeutic candidate for silicosis.

scholarly journals Alleviation of Rosup-induced oxidative stress in porcine granulosa cells by anthocyanins from red-fleshed apples

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0184033 ◽  
Author(s):  
Ya Xiang ◽  
Fangnong Lai ◽  
Guifang He ◽  
Yapeng Li ◽  
Leilei Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Granulosa Cells ◽  
Porcine Granulosa Cells
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