scholarly journals Dynamic Distribution of HIG2A between the Mitochondria and the Nucleus in Response to Hypoxia and Oxidative Stress

2021 ◽  
Vol 23 (1) ◽  
pp. 389
Author(s):  
Celia Salazar ◽  
Miriam Barros ◽  
Alvaro A. Elorza ◽  
Lina María Ruiz
Keyword(s):  
Oxidative Stress ◽  
Cancer Biology ◽  
C2c12 Cells ◽  
Stress Factors ◽  
Hek293 Cells ◽  
Mitochondrial Uncoupling ◽  
Dynamic Distribution ◽  
Protein Levels ◽  
Chemical Hypoxia ◽  
And Oxidative Stress

Mitochondrial respiratory supercomplex formation requires HIG2A protein, which also has been associated with cell proliferation and cell survival under hypoxia. HIG2A protein localizes in mitochondria and nucleus. DNA methylation and mRNA expression of the HIGD2A gene show significant alterations in several cancers, suggesting a role for HIG2A in cancer biology. The present work aims to understand the dynamics of the HIG2A subcellular localization under cellular stress. We found that HIG2A protein levels increase under oxidative stress. H2O2 shifts HIG2A localization to the mitochondria, while rotenone shifts it to the nucleus. HIG2A protein colocalized at a higher level in the nucleus concerning the mitochondrial network under normoxia and hypoxia (2% O2). Hypoxia (2% O2) significantly increases HIG2A nuclear colocalization in C2C12 cells. In HEK293 cells, chemical hypoxia with CoCl2 (>1% O2) and FCCP mitochondrial uncoupling, the HIG2A protein decreased its nuclear localization and shifted to the mitochondria. This suggests that the HIG2A distribution pattern between the mitochondria and the nucleus depends on stress and cell type. HIG2A protein expression levels increase under cellular stresses such as hypoxia and oxidative stress. Its dynamic distribution between mitochondria and the nucleus in response to stress factors suggests a new communication system between the mitochondria and the nucleus.

CTRP3 protects against uric acid-induced endothelial injury by inhibiting inflammation and oxidase stress in rats

2021 ◽  
pp. 153537022110471
Author(s):  
Junxia Zhang ◽  
Xue Lin ◽  
Jinxiu Xu ◽  
Feng Tang ◽  
Lupin Tan
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Specific Inhibitor ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Sprague Dawley ◽  
Protein Levels ◽  
And Oxidative Stress

Hyperuricemia, which contributes to vascular endothelial damage, plays a key role in multiple cardiovascular diseases. This study was designed to investigate whether C1q/tumor necrosis factor (TNF)-related protein 3 (CTRP3) has a protective effect on endothelial damage induced by uric acid and its underlying mechanisms. Animal models of hyperuricemia were established in Sprague-Dawley (SD) rats through the consumption of 10% fructose water for 12 weeks. Then, the rats were given a single injection of Ad-CTRP3 or Ad-GFP. The animal experiments were ended two weeks later. In vitro, human umbilical vein endothelial cells (HUVECs) were first infected with Ad-CTRP3 or Ad-GFP. Then, the cells were stimulated with 10 mg/dL uric acid for 48 h after pretreatment with or without a Toll-like receptor 4 (TLR4)-specific inhibitor. Hyperuricemic rats showed disorganized intimal structures, increased endothelial apoptosis rates, increased inflammatory responses and oxidative stress, which were accompanied by reduced CTRP3 and elevated TLR4 protein levels in the thoracic aorta. In contrast, CTRP3 overexpression decreased TLR4 protein levels and ameliorated inflammatory responses and oxidative stress, thereby improving the morphology and apoptosis of the aortic endothelium in rats with hyperuricemia. Similarly, CTRP3 overexpression decreased TLR4-mediated inflammation, reduced oxidative stress, and rescued endothelial damage induced by uric acid in HUVECs. In conclusion, CTRP3 ameliorates uric acid-induced inflammation and oxidative stress, which in turn protects against endothelial injury, possibly by inhibiting TLR4-mediated inflammation and downregulating oxidative stress.

Relationship between aldose reductase enzyme and the signaling pathway of protein kinase C in an in vitro diabetic retinopathy model

2020 ◽  
Vol 98 (4) ◽  
pp. 243-251
Author(s):  
Mutlu Sarikaya ◽  
Nuray Yazihan ◽  
Net Daş Evcimen
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Signaling Molecules ◽  
Protein Levels ◽  
Kinase C ◽  
The Relationship ◽  
And Oxidative Stress ◽  
Expression And Activity

Protein kinase C (PKC) and aldose reductase (AR) enzyme activities are increased in diabetes and complications are include retinopathy, nephropathy, and neuropathy. However, the relationship between PKC and AR and the underlying molecular mechanisms is still unclear. We aimed to evaluate the relationship between these two enzymes and clarify the underlying molecular mechanisms by the related signaling molecules. The effects of hyperglycemia and oxidative stress on AR and PKC enzymes and the signaling molecules such as nuclear factor-kappa B (NF-κB), inhibitor kappa B-alpha (IkB-α), total c-Jun, phospho c-Jun, and stress-activated protein kinases (SAPK)/Jun amino-terminal kinases (JNK) were evaluated in human retinal pigment epithelial cells (ARPE-19). AR, PKC protein levels, and related signaling molecules increased with hyperglycemia and oxidative stress. The AR inhibitor sorbinil decreased PKC expression and activity and all signaling molecule protein levels. Increased AR expression during hyperglycemia and oxidative stress was found to be correlated with the increase in PKC expression and activity in both conditions. Decreased expression and activity of PKC and the protein levels of related signaling molecules with the AR inhibitor sorbinil showed that AR enzyme may play a key role in the expression of PKC enzyme and oxidative stress during diabetes.

scholarly journals Ent-Peniciherqueinone Suppresses Acetaldehyde-Induced Cytotoxicity and Oxidative Stress by Inducing ALDH and Suppressing MAPK Signaling

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1229
Author(s):  
Taehoon Oh ◽  
Mincheol Kwon ◽  
Jae Sik Yu ◽  
Mina Jang ◽  
Gun-Hee Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Modern Society ◽  
Mapk Signaling ◽  
Heme Oxygenase 1 ◽  
Ros Scavenging ◽  
Protein Levels ◽  
Cellular Reactive Oxygen Species ◽  
Related Stress ◽  
And Oxidative Stress

Studies on ethanol-induced stress and acetaldehyde toxicity are actively being conducted, owing to an increase in alcohol consumption in modern society. In this study, ent-peniciherqueinone (EPQ) isolated from a Hawaiian volcanic soil-associated fungus Penicillium herquei FT729 was found to reduce the acetaldehyde-induced cytotoxicity and oxidative stress in PC12 cells. EPQ increased cell viability in the presence of acetaldehyde-induced cytotoxicity in PC12 cells. In addition, EPQ reduced cellular reactive oxygen species (ROS) levels and restored acetaldehyde-mediated disruption of mitochondrial membrane potential. Western blot analyses revealed that EPQ treatment increased protein levels of ROS-scavenging heme oxygenase-1 and superoxide dismutase, as well as the levels of aldehyde dehydrogenase (ALDH) 1, ALDH2, and ALDH3, under acetaldehyde-induced cellular stress. Finally, EPQ reduced acetaldehyde-induced phosphorylation of p38 and c-Jun N-terminal kinase, which are associated with ROS-induced oxidative stress. Therefore, our results demonstrated that EPQ prevents cellular oxidative stress caused by acetaldehyde and functions as a potent agent to suppress hangover symptoms and alcohol-related stress.

scholarly journals Maggot Extracts Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis via the Activation of Nrf2

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Rong Wang ◽  
Yongzheng Luo ◽  
Yadong Lu ◽  
Daojuan Wang ◽  
Tingyu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Experimental Colitis ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Related Factor ◽  
Protective Effects ◽  
Protein Levels ◽  
Bowel Diseases ◽  
Effective Therapeutic Strategy ◽  
And Oxidative Stress

Ulcerative colitis (UC) is a common chronic remitting disease driven through altered immune responses with production of inflammatory cytokines. Oxidant/antioxidant balance is also suggested to be an important factor for the recurrence and progression of UC. Maggots are known as a traditional Chinese medicine also known as “wu gu chong.” NF-E2-related factor-2 (Nrf2) transcription factor regulates the oxidative stress response and also represses inflammation. The aim of this study was to investigate the effects of maggot extracts on the amelioration of inflammation and oxidative stress in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and evaluate if the maggot extracts could repress inflammation and oxidative stress using RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In the present study, we found that the maggot extracts significantly prevented the loss of body weight and shortening of colon length in UC induced by DSS. Furthermore, DSS-induced expression of proinflammatory cytokines at both mRNA and protein levels in the colon was also attenuated by the maggot extracts. In addition, the maggot extracts could significantly suppress the expression of interleukin- (IL-) 1β, IL-6, TNF-α, NFκB p65, p-IκB, p22-phox, and gp91-phox in LPS-stimulated RAW 264.7 cells and colonic tissues. The maggot extracts increased the level of Nrf2 and prevented the degradation of Nrf2 through downregulating the expression of Keap1, which resulted in augmented levels of HO-1, SOD, and GSH-Px and reduced levels of MPO and MDA. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of the maggot extracts in mice with colitis and RAW 264.7 cells. Taken together, our data for the first time confirmed that the maggot extracts ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf2/HO-1 pathway. This study sheds light on the possible development of an effective therapeutic strategy for inflammatory bowel diseases.

scholarly journals The Effect of Rice Bran Extract on Arterial Blood Pressure, Hepatic Steatosis, and Inflammation in Mice Fed with a High-Fat Diet

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Naphatsanan Duansak ◽  
Pritsana Piyabhan ◽  
Umarat Srisawat ◽  
Jarinyaporn Naowaboot ◽  
Nusiri Lerdvuthisopon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Arterial Blood Pressure ◽  
High Fat Diet ◽  
High Fat ◽  
Protein Levels ◽  
Arterial Blood ◽  
Cox 2 ◽  
And Oxidative Stress

Background. Inflammation and hypertension are primary mechanisms involving in obesity-associated adverse effects of a high-fat diet. The aim of this study was to evaluate the effects of rice bran extract (RBE) on arterial blood pressure, hepatic steatosis, inflammation, and oxidative stress in high-fat diet (HFD)-induced obese mice. Methods. Male ICR mice were divided into four groups, including a normal-diet control group, a high-fat diet (HFD) (60% kcal from fat) group, an HFD group treated with RBE (220 mg/kg/day), and an HFD group treated with 1100 mg/kg/day for eight weeks. Besides body weight and arterial blood pressure, we determined liver values of total cholesterol, triglyceride, as well as percent body fat, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), nuclear factor kappa-B (NF-κB), matrix metalloprotease-9 (MMP-9), cyclooxygenase-2 (COX-2), and mRNA endothelial nitric oxide synthase (eNOS). Results. The HFD group had increased body weight, increased systolic and diastolic blood pressure, liver total cholesterol, triglyceride, NF-κB, COX-2 and MMP-9 protein levels, and decreased mRNA eNOS in the aorta. Mice of the HFD group receiving RBE had reduced diastolic blood pressure, as well as significantly decreased liver and serum TNF-α and MDA levels in the liver, and reduced NF-κB levels in both the liver and heart. Conclusions. These results demonstrate that RBE decreases diastolic blood pressure, the liver lipid droplet accumulation, liver and myocardial NF-κB, myocardial COX-2 and MMP-9 protein levels, and oxidative stress. Moreover, RBE may improve endothelial function and may alleviate adverse health effects associated with obesity including obesity-associated hypertension.

scholarly journals Honokiol Alleviates Methionine-Choline Deficient Diet-Induced Hepatic Steatosis and Oxidative Stress in C57BL/6 Mice by Regulating CFLAR-JNK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ting Zhai ◽  
Wei Xu ◽  
Yayun Liu ◽  
Kun Qian ◽  
Yanling Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Regulatory Gene ◽  
Deficient Diet ◽  
Jnk Pathway ◽  
Beneficial Effects ◽  
Protein Levels ◽  
And Oxidative Stress

Background. Honokiol (HNK) has been reported to possess various beneficial effects in the context of metabolic disorders, including fatty liver, insulin resistance, and oxidative stress which are closely related to nonalcoholic steatohepatitis (NASH), however with no particular reference to CFLAR or JNK. Methods. C57BL/6 mice were fed methionine-choline-deficient (MCD) diet and administered simultaneously with HNK (10 and 20 mg/kg once a day, ig) for 6 weeks, and NCTC1469 cells were pretreated, respectively, by oleic acid (OA, 0.5 mmol/L) plus palmitic acid (PA, 0.25 mmol/L) for 24 h, and adenovirus-down Cflar for 24 h, then exposed to HNK (10 and 20 μmol/L) for 24 h. Commercial kits, H&E, MT, ORO staining, RT-qPCR, and Western blotting were used to detect the biomarkers, hepatic histological changes, and the expression of key genes involved in NASH. Results. The in vivo results showed that HNK suppressed the phosphorylation of JNK (pJNK) by activating CFLAR; enhanced the mRNA expression of lipid metabolism-related genes Acox, Cpt1α, Fabp5, Gpat, Mttp, Pparα, and Scd-1; and decreased the levels of hepatic TG, TC, and MDA, as well as the levels of serum ALT and AST. Additionally, HNK enhanced the protein expression of oxidative stress-related key regulatory gene NRF2 and the activities of antioxidases HO-1, CAT, and GSH-Px and decreased the protein levels of prooxidases CYP4A and CYP2E1. The in vivo effects of HNK on the expression of CLFAR, pJNK, and NRF2 were proved by the in vitro experiments. Moreover, HNK promoted the phosphorylation of IRS1 (pIRS1) in both tested cells and increased the uptake of fluorescent glucose 2-NBDG in OA- and PA-pretreated cells. Conclusions. HNK ameliorated NASH mainly by activating the CFLAR-JNK pathway, which not only alleviated fat deposition by promoting the efflux and β-oxidation of fatty acids in the liver but also attenuated hepatic oxidative damage and insulin resistance by upregulating the expression of NRF2 and pIRS1.

scholarly journals κ-Opioid Receptor Agonist Ameliorates Postoperative Neurocognitive Disorder by Activating the Ca2+/CaMKII/CREB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Guopeng Ding ◽  
Dandan Li ◽  
Yingjie Sun ◽  
Keyan Chen ◽  
Dandan Song
Keyword(s):  
Oxidative Stress ◽  
Cardiopulmonary Bypass ◽  
Brain Injury ◽  
Opioid Receptor ◽  
Stress Factors ◽  
Neurocognitive Disorder ◽  
Apoptosis Rate ◽  
The Brain ◽  
And Oxidative Stress ◽  
Creb Pathway

Objective. Cardiopulmonary bypass (CPB) is an important cardiac operation and also a high-risk procedure, leading to postoperative neurocognitive disorder. However, there are few effective drugs to treat the aftermath of CPB. Therefore, we observe the effect of kappa opioid receptor (KOR) agonist on cognitive disorders of rats after cardiopulmonary bypass (CPB) and investigate the mechanism of the Ca2+/calmodulin-dependent protein kinase (CaMKII)/cAMP responsive element-binding protein (CREB) pathway. Methods. A total of 40 Sprague Dawley rats were randomly divided into the sham operation group (sham group, n = 10), CPB model group (CPB group, n = 10), CPB + KOR agonist U50488H group (UH group, n = 10), and CPB + specific CaMKII antagonist + U50488H group (CKU group, n = 10). The changes in the rats’ cognitive function were evaluated using the Morris water maze, the hippocampal histopathological changes were observed via hematoxylin-eosin (H&E) staining, and the apoptosis rate of neuronal cells was detected through terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Moreover, enzyme-linked immunosorbent assay (ELISA) was applied to examine the changes in brain injury markers, inflammatory factors, and oxidative stress factors. The hippocampal variations in Ca2+ concentration and oxidative stress index (ROS) levels were measured by immunofluorescence staining, and western blotting was performed to determine the expression changes in the Ca2+/CaMKII/CREB pathway. Results. The KOR agonist could shorten latency, increase the swimming distance and residence time in the target quadrant, and ameliorate postoperative neurocognitive disorder (PND). Meanwhile, the KOR agonist relieved CPB-induced hippocampal and oxidative stress injuries, reduced NSE and S-100β expression, decreased the apoptosis rate, and repressed the inflammatory response, which alleviated the brain injury. In addition, U50488H was able to decrease Ca2+ influx and glutamate (Glu) level, inhibit N-methyl-D-aspartate receptor (NMDAR) expression, upregulate CaMKII expression, promote CREB phosphorylation, and increase the brain-derived neurotrophic factor (BDNF) level in CPB rats. However, the protective effects of KORs against PND were suppressed following the application of the CaMKII-specific antagonist. Conclusion. The KOR agonist activates the Ca2+/CaMKII/CREB pathway, which improves the brain injury and relieves PND in CPB rats.

scholarly journals Effect of Carthamus Tinctorius Safflower Aqueous Extract Against Nickel Chloride Induces Hematotoxicity and Immunotoxicity in Adult Male Rabbits

2017 ◽  
Vol 30 (3) ◽  
pp. 19
Author(s):  
Layla Abd-Al-Sattar Sadiq Laylani
Keyword(s):  
Oxidative Stress ◽  
Aqueous Extract ◽  
Blood Cells ◽  
Hematological Parameters ◽  
Nickel Chloride ◽  
Carthamus Tinctorius ◽  
Stress Factors ◽  
Control Group ◽  
Immunological Parameters ◽  
And Oxidative Stress

  This study was designed to show, the role of Carthamus tinctorius safflower aqueous extract against toxicity of nickel chloride (NiCl2). Twenty male, rabbits were used and divided into four groups (with 5 rabbits in each group); group (control group) received normal diet, group II received orally 100mg/kg NiCl2 for six weeks, group III received 100mg/kg NiCl2 and 100mg/kg extract six weeks, group IV received 100mg/kg NiCl2 and 200mg/ kg extract six weeks. Hematological parameters showed (RBC (Red blood cells), Hb (Hemoglobin), PCV (Packed cells volume) decreased and WBC (White blood cells) increased) significant changes (P < 0.05) compared with control group. Immunological parameters (IgG, IgA and IgM increased) and oxidative stress factors (MDA increased and GSH decreased) show significant changes (P < 0.05) compared with control group. While, safflower aqueous adverse the negative effects of NiCl2 and causing ameliorative effects on all hematological parameters, hematological immunological parameters and oxidative stress factors showed no significant changes (P < 0.05) compared with control group. It was concluded that flower extract of Carthamus tinctorius has been antioxidant role against nickel chloride toxicity in rabbits.  

scholarly journals Biochemical and immunological investigation of fascioliasis in cattle in Egypt

2020 ◽  
Vol 13 (5) ◽  
pp. 923-930
Author(s):  
Nani Nasreldin ◽  
Rania Samir Zaki
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Meat Quality ◽  
Stress Factors ◽  
Postmortem Changes ◽  
Immunological Parameters ◽  
Serum Biochemical ◽  
Fasciola Spp ◽  
Glutamyl Transferase ◽  
And Oxidative Stress

Background and Aim: Fasciola hepatica and Fasciola gigantica are two commonly reported liver flukes that cause fascioliasis in ruminants. Among the members of the genus Fasciola, F. hepatica was identified in the study area. Fascioliasis is a major disease that affects the production of livestock by causing liver damage. F. hepatica has developed advanced mechanisms to trick, elude, and alter the host immune response, similar to an extrinsic stressor. These mechanisms consequently affect the animals' physiological and metabolic functions in vivo and postmortem changes, which have significant influences on animal welfare and meat quality development. Therefore, this study aimed to determine the current prevalence of cattle fascioliasis at abattoirs in El-Kharga city, New Valley Governorate, Egypt, and to investigate the changes in serum biochemical and immunological parameters and oxidative stress factors due to Fasciola spp. infection in terms of meat quality and immune response. Materials and Methods: A total of 226 cattle were inspected for the presence of Fasciola spp. The liver of each cattle was examined by making several incisions for detecting adult Fasciola spp. in El- Kharga . The blood samples were collected to analyze the changes in serum biochemical and immunological parameters and oxidative stress factors. Results: Of the 226 cattle, 38 (16.81%) were positive for F. hepatica at the postmortem examination. Cattle infected with F. hepatica had highly elevated serum alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, γ-glutamyl transferase, urea, and creatinine levels. Immunological cytokine profiles showed significantly increased serum interleukin (IL)-4, IL-10, and transforming growth factor-beta levels and a significantly decreased interferon-γ level. Furthermore, oxidative stress profiles showed significantly increased serum malondialdehyde and nitric oxide levels and significantly decreased total antioxidant capacity and reduced glutathione level. Conclusion: This study demonstrated that F. hepatica infection alone is an oxidative stress factor that affects slaughtered animals, leading to biochemical and metabolic alterations in the early postmortem period.

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