Contribution of PPARγ in modulation of acrolein-induced inflammatory signaling in gp91phox knock-out mice

2017 ◽  
Vol 95 (4) ◽  
pp. 482-490 ◽  
Author(s):  
Zivar Yousefipour ◽  
Neha Chug ◽  
Katarzyna Marek ◽  
Alicia Nesbary ◽  
Joseph Mathew ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Mass ◽  
Total Antioxidant Status ◽  
Peroxisome Proliferator ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Knock Out ◽  
Total Antioxidant ◽  
In The Wild ◽  
Knock Out Mice

Oxidative stress and inflammation are major contributors to acrolein toxicity. Peroxisome proliferator activated receptor gamma (PPARγ) has antioxidant and anti-inflammatory effects. We investigated the contribution of PPARγ ligand GW1929 to the attenuation of oxidative stress in acrolein-induced insult. Male gp91phox knock-out (KO) mice were treated with acrolein (0.5 mg·(kg body mass)–1 by intraperitoneal injection for 7 days) with or without GW1929 (GW; 0.5 mg·(kg body mass)–1·day–1, orally, for 10 days). The livers were processed for further analyses. Acrolein significantly increased 8-isoprostane and reduced PPARγ activity (P < 0.05) in the wild type (WT) and KO mice. GW1929 reduced 8-isoprostane (by 32% and 40% in WT and KO mice, respectively) and increased PPARγ activity (by 81% and 92% in WT and KO, respectively). Chemokine activity was increased (by 63%) in acrolein-treated WT mice, and was reduced by GW1929 (by 65%). KO mice exhibited higher xanthine oxidase (XO). Acrolein increased XO and COX in WT mice and XO in KO mice. GW1929 significantly reduced COX in WT and KO mice and reduced XO in KO mice. Acrolein significantly reduced the total antioxidant status in WT and KO mice (P < 0.05), which was improved by GW1929 (by 75% and 74%). The levels of NF-κB were higher in acrolein-treated WT mice. GW1929 reduced NF-κB levels (by 51%) in KO mice. Acrolein increased CD36 in KO mice (by 43%), which was blunted with GW1929. Data confirms that the generation of free radicals by acrolein is mainly through NAD(P)H, but other oxygenates play a role too. GW1929 may alleviate the toxicity of acrolein by attenuating NF-κB, COX, and CD36.

scholarly journals The Transcriptional Response to a Peroxisome Proliferator-activated Receptor α Agonist Includes Increased Expression of Proteome Maintenance Genes

2004 ◽  
Vol 279 (50) ◽  
pp. 52390-52398 ◽  
Author(s):  
Steven P. Anderson ◽  
Paul Howroyd ◽  
Jie Liu ◽  
Xun Qian ◽  
Rainer Bahnemann ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Transcriptional Response ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Proteasomal Genes ◽  
Oxidative Stress Responses

The nuclear receptor peroxisome proliferator-activated receptor α (PPARα), in addition to regulating lipid homeostasis, controls the level of tissue damage after chemical or physical stress. To determine the role of PPARα in oxidative stress responses, we examined damage after exposure to chemicals that increase oxidative stress in wild-type or PPARα-null mice. Primary hepatocytes from wild-type but not PPARα-null mice pretreated with the PPAR pan-agonist WY-14,643 (WY) were protected from damage to cadmium and paraquat. The livers from intact wild-type but not PPARα-null mice were more resistant to damage after carbon tetrachloride treatment. To determine the molecular basis of the protection by PPARα, we identified by transcript profiling genes whose expression was altered by a 7-day exposure to WY in wild-type and PPARα-null mice. Of the 815 genes regulated by WY in wild-type mice (p≤ 0.001; ≥1.5-fold or ≤-1.5-fold), only two genes were regulated similarly by WY in PPARα-null mice. WY increased expression of stress modifier genes that maintain the health of the proteome, including those that prevent protein aggregation (heat stress-inducible chaperones) and eliminate damaged proteins (proteasome components). Although the induction of proteasomal genes significantly overlapped with those regulated by 1,2-dithiole-3-thione, an activator of oxidant-inducible Nrf2, WY increased expression of proteasomal genes independently of Nrf2. Thus, PPARα controls the vast majority of gene expression changes after exposure to WY in the mouse liver and protects the liver from oxidant-induced damage, possibly through regulation of a distinct set of proteome maintenance genes.

scholarly journals Total Antioxidant Status (TAS), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) in Oropharyngeal Cancer Associated with EBV Infection

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Małgorzata Strycharz-Dudziak ◽  
Małgorzata Kiełczykowska ◽  
Bartłomiej Drop ◽  
Łukasz Świątek ◽  
Ewa Kliszczewska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oropharyngeal Cancer ◽  
Epstein Barr Virus ◽  
Total Antioxidant Status ◽  
Wild Type ◽  
Early Antigen ◽  
Barr Virus ◽  
Ebv Infection ◽  
Total Antioxidant ◽  
Epstein Barr

A growing number of studies reveal that oxidative stress is associated with viral infections or cancer development. However, there are few reports assessing the relationships between oxidative stress, viral infection, and carcinogenesis. The present study analyzed the level of total antioxidant status (TAS) as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in patients with oropharyngeal cancer both Epstein-Barr virus (EBV)-positive and EBV-negative in comparison with the control group. The correlations between these parameters and EBV type (wild-type LMP1 (wt-LMP1) or LMP1 with deletion (del-LMP1)), level of antibodies against EBV, the degree of tumor differentiation, and TNM classification were also investigated. Fresh frozen tumor tissue samples collected from 66 patients with oropharyngeal squamous cell carcinoma were tested using nested PCR assay for EBV DNA detection. Spectrophotometric methods were used to measure TAS values as well as SOD and GPx activities in homogenates of tissue, using diagnostic kits produced by Randox Laboratories. Sera from all individuals were investigated using ELISA method to detect the presence of Epstein-Barr virus capsid antigen (EBVCA) IgM and IgG, Epstein-Barr virus nuclear antigen (EBNA) IgG, and early antigen (EA) IgG antibodies. The level of TAS and activities of antioxidant enzymes (GPx and SOD) were significantly decreased in tissues with oropharyngeal cancer, particularly in EBV-positive cases. In 82.3% of patients, wt-LMP1 was detected. Significantly lower TAS, GPx, and SOD values were stated in patients infected with wild-type EBV. The presence of antibodies against early antigen (anti-EA) was detected in over 80% of patients, which suggests reactivation of EBV infection. The correlation between the degree of tumor differentiation and TN classification, especially in EBV-positive patients, was also observed. Determination of these parameters may be useful in evaluating tumor burden in patients with various stages of oropharyngeal cancer and could be an important prognostic factor. Future studies are needed to understand the role of EBV lytic reactivation induced by oxidative stress.

Branched-chain amino acids regulate hyaluronan synthesis and PPARα expression in the skin

2021 ◽  
Author(s):  
Takumi Yamane ◽  
Yasuyuki Kitaura ◽  
Ken Iwatsuki ◽  
Yoshiharu Shimomura ◽  
Yuichi Oishi
Keyword(s):  
Branched Chain Amino Acids ◽  
Peroxisome Proliferator ◽  
Keto Acid ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Branched Chain Amino Acid ◽  
Key Enzyme ◽  
In The Wild ◽  
Branched Chain ◽  
Gene Expression Levels

Abstract We examined the effects of deletion of branched-chain α-keto acid dehydrogenase kinase (BDK), a key enzyme in branched-chain amino acid catabolism, on hyaluronan synthesis in mice. The skin levels of hyaluronan and the gene expression levels of hyaluronan synthase (Has)2, Has3 and peroxisome proliferator-activated receptor-α (PPARα) were significantly lower in the BDK-knockout group than in the wild type group.

scholarly journals Body mass index is associated with interleukin-1, adiponectin, oxidative stress and ioduria levels in healthy adults

2018 ◽  
Vol 35 (4) ◽  
pp. 841 ◽  
Author(s):  
Saytin Cruz-Mejía ◽  
Henri Hamil Durán López ◽  
Mónica Navarro Meza ◽  
Irene Xochihua Rosas ◽  
Sol De la Peña ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Mass Index ◽  
Body Mass ◽  
Antioxidant Status ◽  
Interleukin 1 ◽  
Total Antioxidant Status ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Total Antioxidant ◽  
Obese Subjects

Background: iodine contributes to maintain the balance of the reduced and oxidized species and is also required for thyroid hormones synthesis as triiodothyronine (T3), which regulates energy metabolism in adults. Increased body mass index (BMI) is associated with inflammatory markers, oxidative stress, and abnormalities in adipocytokines secretions that are associated with obesity and chronic disease.Objective: the aim of the study is to investigate the association between ioduria, oxidative stress, total antioxidant status, adiponectin and interleukin-1 (IL-1) with BMI in healthy adults.Methods: a cross-sectional study was performed in 114 healthy adult volunteers, aged 25-44 years, divided according to their BMI in three groups: normal weight (BMI < 25), overweight (BMI ≤ 25 to < 30), obesity (BMI ≥ 30). Adiponectin and IL-1 were measured by immune-enzymatic assays; oxidative stress, by determination of malondialdehyde (MDA); and total antioxidant status (TAS) and ioduria were measured by colorimetric assays. Statistical association was done by Spearman’s test.Results: overweight and obese subjects have higher serum levels of MDA, TAS and IL-1 vs normal weight subjects. Moreover, overweight and obese subjects have lower levels of iodine and adiponectin vs normal weight subjects. MDA was positively related only with obese subjects (r = 0.787, p = 0.008) and TAS with overweight (r = 0.398, p = 0.049) and obese subjects (r = 0.448, p = 0.030). In contrast, a reverse correlation with ioduria was found in obese subjects (r = 0.463, p = 0.001). Adiponectin was negatively related only in obese subjects (r = -0.477, p = 0.001), while, IL-1 was positively related with the increase of BMI (overweight r = 0.287, p = 0.050; and obesity r = 0.515, p = 0.006).Conclusion: alteration in IL-1, adiponectin and oxidative stress levels were found to be related to overweight and obesity; also, iodine levels decreased when BMI increased, contributing to loss of redox equilibrium. All this data may play an important role in etiopathogenesis of chronic disease related to the increase of BMI.

scholarly journals Metabolomic and Lipidomic Analysis of the Heart of Peroxisome Proliferator-Activated Receptor-γ Coactivator 1-β Knock Out Mice on a High Fat Diet

Metabolites ◽  
2012 ◽  
Vol 2 (2) ◽  
pp. 366-381 ◽  
Author(s):  
Gregor McCombie ◽  
Gema Medina-Gomez ◽  
Christopher J Lelliott ◽  
Antonio Vidal-Puig ◽  
Julian L Griffin
Keyword(s):  
High Fat Diet ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Knock Out ◽  
Lipidomic Analysis ◽  
Knock Out Mice

Abstract 365: Differential Regulation of NOX2, NOX4 and SOD Expression in the Heart and Kidneys by PPAR-α During Angiotensin II Hypertension

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Justin L Wilson ◽  
Kavitha Sankavaram ◽  
Rong Duan ◽  
Joanne S Allard ◽  
Dexter L Lee
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Mean Arterial Pressure ◽  
Control Period ◽  
Differential Regulation ◽  
Peroxisome Proliferator ◽  
Ang Ii ◽  
Wild Type ◽  
Sod Activity ◽  
Peroxisome Proliferator Activated Receptor

Previous reports suggest peroxisome proliferator-activated receptor-α (PPAR-α) agonist attenuates hypertension by suppressing oxidative stress and increasing superoxide dismutase (SOD) activity. We tested the hypothesis that the absence of PPAR-α would increase NADPH oxidase (NOX)2, NOX4 and decrease SOD expression in mice heart and kidneys during Ang II hypertension. Male (10 - 12 weeks old) PPAR-α knockout (KO) mice and their wild-type (WT) controls were implanted with biotelemetry devices and infused with a slow pressor dose of Ang II (400 ng/kg/min) for 12 days. Separate groups of KO + Ang II and WT + Ang II mice were given the NOX inhibitor, apocynin (1 g/L) or PPAR-α agonist, fenofibrate (145 mg/kg/day). Mean arterial pressure (MAP) was similar between KO (119 ± 2 mmHg) and WT (122 ± 2 mmHg) during the control period. On day 12 of Ang II, MAP was significantly higher in KO than WT, 161 ± 5 and 145 ± 4 mmHg, respectively. Fenofibrate significantly reduced MAP in WT + Ang II mice (134 ± 5 mmHg) and apocynin reduced MAP in KO + Ang II and WT + Ang II mice. Heart and kidney NOX2 expression were significantly increased (61 ± 5% and 33 ± 5 %, respectively) in KO + Ang II when compared to WT + Ang II mice. Apocynin treatment significantly reduced heart and kidney NOX2 expression in KO + Ang II mice. Heart NOX4 expression was significantly decreased (28 ± 3%) in WT + Ang II mice when compared to WT controls. No significant changes were observed in KO + Ang II heart NOX4 expression. Kidney NOX4 expression was significantly decreased in both Ang II-treated KO (77 ± 5%) and WT (50 ± 5%) mice when compared to their respective controls. WT + Ang II SOD expression in the heart was significantly lower than WT controls. Ang II did not lower heart SOD expression in KO mice. SOD expression in the kidneys was significantly decreased in KO + Ang II and WT + Ang II when compared to their respective controls. Fenofibrate significantly increased kidney SOD expression in WT + Ang II mice above WT controls. Fenofibrate did not significantly increase kidney SOD expression in KO + Ang II mice above KO controls. Our results suggest that increased heart and kidney NOX2 expression, along with decreased SOD expression in PPAR-α KO mice contributes to significant increases in MAP during Ang II hypertension.

scholarly journals Peroxisome Proliferator-Activated Receptor Gamma Exacerbates Concanavalin A-Induced Liver Injury via Suppressing the Translocation of NF-κB into the Nucleus

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Yuji Ogawa ◽  
Masato Yoneda ◽  
Wataru Tomeno ◽  
Kento Imajo ◽  
Yoshiyasu Shinohara ◽  
...  
Keyword(s):  
Liver Injury ◽  
Concanavalin A ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Peroxisome Proliferator ◽  
Con A ◽  
Mobility Shift ◽  
Peroxisome Proliferator Activated Receptor ◽  
Knock Out ◽  
In The Wild ◽  
Mobility Shift Assay

Peroxisome proliferator-activated receptor-γ(PPARγ) has been reported to reduce inflammation and attenuate fibrosis in the liver. In this study, we investigated the effects of PPARγon the liver injury induced by 20 mg/kg Concanavalin A (Con A). The mice were administered one of the three types of PPARγligands (pioglitazone, ciglitazone, and troglitazone) for 1 week, and the serum alanine aminotransferase (ALT) levels at 20 h after Con A injection were significantly elevated in the PPARγligand-treated mice. Furthermore, the serum ALT levels after Con A injection in the PPARγhetero-knock-out mice (PPARγ+/−mice) were lower than those in the wild-type mice (WT mice). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) revealed extensive liver damage induced by Con A in the pioglitazone-treated mice. Electrophoresis mobility shift assay (EMSA) revealed that activation of translocation of nuclear factor- (NF-)κB, which is a suppressor of apoptosis, in the nucleus of the hepatocytes was suppressed in the pioglitazone-treated mice after Con A injection. In this study, we showed that PPARγexacerbated Con A-induced liver injury via suppressing the translocation of NF-κB into the nucleus, thereby inhibiting the suppression of liver cell apoptosis.

scholarly journals Studies in a Murine Granuloma Model of Instilled Carbon Nanotubes: Relevance to Sarcoidosis

2021 ◽  
Vol 22 (7) ◽  
pp. 3705
Author(s):  
Barbara P. Barna ◽  
Anagha Malur ◽  
Mary Jane Thomassen
Keyword(s):  
Carbon Nanotubes ◽  
Inflammatory Mediators ◽  
Inflammatory Responses ◽  
Multiwall Carbon Nanotubes ◽  
Peroxisome Proliferator ◽  
Granulomatous Disease ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Knock Out ◽  
Pulmonary Granuloma

Poorly soluble environmental antigens, including carbon pollutants, are thought to play a role in the incidence of human sarcoidosis, a chronic inflammatory granulomatous disease of unknown causation. Currently, engineered carbon products such as multiwall carbon nanotubes (MWCNT) are manufactured commercially and have been shown to elicit acute and chronic inflammatory responses in experimental animals, including the production of granulomas or fibrosis. Several years ago, we hypothesized that constructing an experimental model of chronic granulomatosis resembling that associated with sarcoidosis might be achieved by oropharyngeal instillation of MWCNT into mice. This review summarizes the results of our efforts to define mechanisms of granuloma formation and identify potential therapeutic targets for sarcoidosis. Evidence is presented linking findings from the murine MWCNT granuloma model to sarcoidosis pathophysiology. As our goal was to determine what pulmonary inflammatory pathways might be involved, we utilized mice of knock-out (KO) backgrounds which corresponded to deficiencies noted in sarcoidosis patients. A primary example of this approach was to study mice with a myeloid-specific knock-out of the lipid-regulated transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) which is strikingly depressed in sarcoidosis. Among the major findings associated with PPARγ KO mice compared to wild-type were: (1) exacerbation of granulomatous and fibrotic histopathology in response to MWCNT; (2) elevation of inflammatory mediators; and (3) pulmonary retention of a potentially antigenic ESAT-6 peptide co-instilled with MWCNT. In line with these data, we also observed that activation of PPARγ in wild-type mice by the PPARγ-specific ligand, rosiglitazone, significantly reduced both pulmonary granuloma and inflammatory mediator production. Similarly, recognition of a deficiency of ATP-binding cassette (ABC) lipid transporter ABCG1 in sarcoidosis led us to study MWCNT instillation in myeloid-specific ABCG1 KO mice. As anticipated, ABCG1 deficiency was associated with larger granulomas and increased levels of inflammatory mediators. Finally, a transcriptional survey of alveolar macrophages from MWCNT-instilled wild-type mice and human sarcoidosis patients revealed several common themes. One of the most prominent mediators identified in both human and mouse transcriptomic analyses was MMP12. Studies with MMP12 KO mice revealed similar acute reactions to those in wild-type but at chronic time points where wild-type maintained granulomatous disease, resolution occurred with MMP12 KO mice suggesting MMP12 is necessary for granuloma progression. In conclusion, these studies suggest that the MWCNT granuloma model has relevance to human sarcoidosis study, particularly with respect to immune-specific pathways.

Association between calcitriol and paricalcitol with oxidative stress in patients with hemodialysis

2020 ◽  
pp. 1-8
Author(s):  
Hasan Haci Yeter ◽  
Berfu Korucu ◽  
Elif Burcu Bali ◽  
Ulver Derici
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Antioxidant Status ◽  
Total Antioxidant Status ◽  
Stress Index ◽  
Total Oxidant Status ◽  
Vitamin D Analog ◽  
Total Antioxidant ◽  
Oxidant Status ◽  
And Oxidative Stress

Abstract. Background: The pathophysiological basis of chronic kidney disease and its complications, including cardiovascular disease, are associated with chronic inflammation and oxidative stress. We investigated the effects of active vitamin D (calcitriol) and synthetic vitamin D analog (paricalcitol) on oxidative stress in hemodialysis patients. Methods: This cross-sectional study was composed of 83 patients with a minimum hemodialysis vintage of one year. Patients with a history of any infection, malignancy, and chronic inflammatory disease were excluded. Oxidative markers (total oxidant and antioxidant status) and inflammation markers (C-reactive protein and interleukin-6) were analyzed. Results: A total of 47% (39/83) patients were using active or analog vitamin D. Total antioxidant status was significantly higher in patients with using active or analog vitamin D than those who did not use (p = 0.006). Whereas, total oxidant status and oxidative stress index were significantly higher in patients with not using vitamin D when compared with the patients who were using vitamin D preparation (p = 0.005 and p = 0.004, respectively). On the other hand, total antioxidant status, total oxidant status, and oxidative stress index were similar between patients who used active vitamin D or vitamin D analog (p = 0.6; p = 0.4 and p = 0.7, respectively). Conclusion: The use of active or selective vitamin D analog in these patients decreases total oxidant status and increases total antioxidant status. Also, paricalcitol is as effective as calcitriol in decreasing total oxidant status and increasing total antioxidant status in patients with chronic kidney disease.

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