scholarly journals An In Vitro Study on Mitochondrial Compensatory Response Induced by Gliadin Peptides in Caco-2 Cells

2019 ◽  
Vol 20 (8) ◽  
pp. 1862 ◽  
Author(s):  
Orlando ◽  
Chimienti ◽  
Pesce ◽  
Fracasso ◽  
Lezza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Vitro Study ◽  
Peroxisome Proliferator ◽  
Compensatory Response ◽  
Peroxisome Proliferator Activated Receptor ◽  
Strand Breaks ◽  
Abasic Sites ◽  
D Loop ◽  
Gliadin Peptides

Dietary gliadin may show a broad spectrum of toxicity. The interplay between mitochondria and gliadin-induced oxidative stress has not been thoroughly examined in the intestinal epithelium. In this kinetic study, Caco-2 cells were exposed for 24 h to pepsin-trypsin-digested gliadin, alone or in combination with the antioxidant 2,6-di-tbutyl-p-cresol (BHT), and the effects on mitochondrial biogenesis and mtDNA were studied. Cells ability to recover from stress was determined after 24 h and 48 h of incubation in the culture medium. Gliadin-induced oxidative stress evoked a compensatory response. The stressor triggered a rapid and significant increase of Peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and Peroxiredoxin III (PrxIII) proteins, and mtDNA amount. As for the effects of gliadin on mtDNA integrity, strand breaks, abasic sites, and modified bases were analyzed in three mtDNA regions. D-loop appeared a more fragile target than Ori-L and ND1/ND2. The temporal trend of the damage at D-loop paralleled that of the amount of mtDNA. Overall, a trend toward control values was shown 48 h after gliadin exposure. Finally, BHT was able to counteract the effects of gliadin. Results from this study highlighted the effects of gliadin-induced oxidative stress on mitochondria, providing valuable evidence that might improve the knowledge of the pathophysiology of gluten-related disorders.

scholarly journals Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Yan ◽  
Si-Chi Xu ◽  
Chun-Yan Kong ◽  
Xiao-Yang Zhou ◽  
Zhou-Yan Bian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Injury ◽  
Inflammatory Factors ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Myocardial Oxidative Stress

Background. Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice. Methods. To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection. Results. Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-γ (PPAR-γ), and the protective effects of piperine were abolished by the treatment of the PPAR-γ antagonist in vivo and in vitro. Conclusions. Piperine could suppress DOX-related cardiac injury via activation of PPAR-γ in mice.

scholarly journals Glucose deprivation, oxidative stress and peroxisome proliferator-activated receptor-α (PPARA) cause peroxisome proliferation in preimplantation mouse embryos

Reproduction ◽  
2009 ◽  
Vol 138 (3) ◽  
pp. 493-505 ◽  
Author(s):  
Sarah Jansen ◽  
Kara Cashman ◽  
Jeremy G Thompson ◽  
Marie Pantaleon ◽  
Peter L Kaye
Keyword(s):  
Oxidative Stress ◽  
Ex Vivo ◽  
Glucose Deprivation ◽  
Mouse Embryos ◽  
Peroxisome Proliferator ◽  
Ros Production ◽  
Peroxisome Proliferator Activated Receptor ◽  
Preimplantation Mouse ◽  
Proliferation Response

Ex vivotwo-cell mouse embryos deprived of glucosein vitrocan develop to blastocysts by increasing their pyruvate consumption; however, zygotes when glucose-deprived cannot adapt this metabolic profile and degenerate as morulae. Prior to their death, these glucose-deprived morulae exhibit upregulation of the H+-monocarboxylate co-transporter SLC16A7 and catalase, which partly co-localize in peroxisomes. SLC16A7 has been linked to redox shuttling for peroxisomal β-oxidation. Peroxisomal function is unclear during preimplantation development, but as a peroxisomal transporter in embryos, SLC16A7 may be involved and influenced by peroxisome proliferators such as peroxisome proliferator-activated receptor-α (PPARA). PCR confirmedPparamRNA expression in mouse embryos. Zygotes were cultured with or without glucose and with the PPARA-selective agonist WY14643 and the developing embryos assessed for expression of PPARA and phospho-PPARA in relation to the upregulation of SLC16A7 and catalase driven by glucose deprivation, indicative of peroxisomal proliferation. Reactive oxygen species (ROS) production and relationship to PPARA expression were also analysed. In glucose-deprived zygotes, ROS was elevated within 2 h, as were PPARA expression within 8 h and catalase and SLC16A7 after 12–24 h compared with glucose-supplied embryos. Inhibition of ROS production prevented this induction of PPARA and SLC16A7. Selective PPARA agonism with WY14643 also induced SLC16A7 and catalase expression in the presence of glucose. These data suggest that glucose-deprived cleavage stage embryos, although supplied with sufficient monocarboxylate-derived energy, undergo oxidative stress and exhibit elevated ROS, which in turn upregulates PPARA, catalase and SLC16A7 in a classical peroxisomal proliferation response.

scholarly journals Diabetic human adipose tissue-derived mesenchymal stem cells fail to differentiate in functional adipocytes

2016 ◽  
Vol 242 (10) ◽  
pp. 1079-1085 ◽  
Author(s):  
Ignazio Barbagallo ◽  
Giovanni Li Volti ◽  
Fabio Galvano ◽  
Guido Tettamanti ◽  
Francesca R Pluchinotta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
In Vitro Study ◽  
Human Adipose Tissue ◽  
Sirtuin 1 ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Adipose tissue dysfunction represents a hallmark of diabetic patients and is a consequence of the altered homeostasis of this tissue. Mesenchymal stem cells (MSCs) and their differentiation into adipocytes contribute significantly in maintaining the mass and function of adult adipose tissue. The aim of this study was to evaluate the differentiation of MSCs from patients suffering type 2 diabetes (dASC) and how such process results in hyperplasia or rather a stop of adipocyte turnover resulting in hypertrophy of mature adipocytes. Our results showed that gene profile of all adipogenic markers is not expressed in diabetic cells after differentiation indicating that diabetic cells fail to differentiate into adipocytes. Interestingly, delta like 1, peroxisome proliferator-activated receptor alpha, and interleukin 1β were upregulated whereas Sirtuin 1 and insulin receptor substrate 1 gene expression were found downregulated in dASC compared to cells obtained from healthy subjects. Taken together our data indicate that dASC lose their ability to differentiate into mature and functional adipocytes. In conclusion, our in vitro study is the first to suggest that diabetic patients might develop obesity through a hypertrophy of existing mature adipocytes due to failure turnover of adipose tissue. Impact statement In the present manuscript, we evaluated the differentiative potential of mesenchymal stem cells (MSCs) in adipocytes obtained from healthy and diabetic patients. This finding could be of great potential interest for the field of obesity in order to exploit such results to further understand the pathophysiological processes underlying metabolic syndrome. In particular, inflammation in diabetic patients causes a dysfunction in MSCs differentiation and a decrease in adipocytes turnover leading to insulin resistance.

scholarly journals Curcumin Eliminates Leptin’s Effects on Hepatic Stellate Cell Activation via Interrupting Leptin Signaling

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3011-3020 ◽  
Author(s):  
Youcai Tang ◽  
Shizhong Zheng ◽  
Anping Chen
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Leptin Receptor ◽  
De Novo ◽  
Stellate Cell ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Leptin Signaling ◽  
Liver Fibrogenesis

Nonalcoholic steatohepatitis (NASH) is commonly found in patients with obesity and is often accompanied with abnormally elevated levels of plasma leptin, i.e. hyperleptinemia. A relatively high population of NASH patients develops hepatic fibrosis, even cirrhosis. Hepatic stellate cells (HSCs) are the major effector cells during liver fibrogenesis and could be activated by leptin. The antioxidant curcumin, a phytochemical from turmeric, has been shown to suppress HSC activation in vitro and in vivo. This project is to evaluate the effect of curcumin on leptin-induced HSC activation and to elucidate the underlying mechanisms. We hypothesize that curcumin abrogates the stimulatory effect of leptin on HSC activation by interrupting leptin signaling and attenuating leptin-induced oxidative stress. Curcumin eliminates the stimulatory effects of leptin on regulating expression of genes closely relevant to HSC activation. Curcumin interrupts leptin signaling by reducing phosphorylation levels of leptin receptor (Ob-R) and its downstream intermediators. In addition, curcumin suppresses gene expression of Ob-R in HSCs, which requires the activation of endogenous peroxisome proliferator-activated receptor-γ and de novo synthesis of glutathione. In conclusion, our results demonstrate that curcumin abrogates the stimulatory effect of leptin on HSC activation in vitro by reducing the phosphorylation level of Ob-R, stimulating peroxisome proliferator-activated receptor-γ activity, and attenuating oxidative stress, leading to the suppression of Ob-R gene expression and interruption of leptin signaling. These results provide novel insights into therapeutic mechanisms of curcumin in inhibiting HSC activation and intervening liver fibrogenesis associated with hyperleptinemia in NASH patients.

scholarly journals SIRT3-dependent mitochondrial oxidative stress in sodium fluoride-induced hepatotoxicity and salvage by melatonin

2017 ◽  
Author(s):  
Chao Song ◽  
Jiamin Zhao ◽  
Jingcheng Zhang ◽  
Tingchao Mao ◽  
Beibei Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Binding Activity ◽  
Daily Injection ◽  
Mechanistic Study ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor

AbstractOxidative stress induced by fluoride (F) is associated with fluorosis formation, but the underlying molecular mechanism remains unclear. In this study, Melatonin pretreatment suppressed F-induced hepatocyte injury in HepG2 cells. Melatonin increases the activity of superoxide dismutase (SOD2) by enhancing sirtuin 3 (SIRT3)-mediated deacetylation and promotes SOD2 gene expression via SIRT3-regulated DNA-binding activity of forkhead box O3 (FoxO3a), indicating that melatonin markedly enhanced mROS scavenging in F-exposed HepG2 cells. Notably, melatonin activated the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α). PGC-1α interacted with the estrogen-related receptor alpha (ERRα) bound to the SIRT3 promoter, where it functions as a transcription factor to regulate SIRT3 expression. Furthermore, daily injection of melatonin for 30 days inhibited F-induced oxidative stress in mice liver, leading to improvement of liver function. Mechanistic study revealed that the protective effects of melatonin were associated with down-regulation of JNK1/2 phosphorylation in vitro and in vivo. Collectively, our data suggest a novel role of melatonin in preventing F-induced oxidative stress through activation of the SIRT3 pathway.

scholarly journals N-Acetylcysteine Inhibits Lipids Production in Mature Adipocytes through the Inhibition of Peroxisome Proliferator-Activated Receptor 

2020 ◽  
pp. 17-29
Author(s):  
Daniela Soto ◽  
Claudia Martini ◽  
Evelyn Frontera ◽  
Laura Montaldo ◽  
Maria C. Vila ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Nutritional Supplement ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mrna And Protein Expression ◽  
Species Production ◽  
Lipids Production

Aims: Reports regarding the effects of antioxidants in obesity have been contradictory. Antioxidant N-acetylcysteine is usually considered a nutritional supplement. Our aim is to evaluate bioactivity of N-acetylcysteine (NAC) on mature adipocytes, which is a close model to in vivo condition. Study Design: In vitro study. Place and Duration of Study: Department of Basic Science (Universidad Nacional de Lujan), Department of Chemical Biology (Universidad de Buenos Aires), CONICET – INEDES and CONICET – IQUIBICEN, between March 2017 and June 2019. Methodology: We evaluated the bioactivity of different concentrations of NAC for 5 days (0.01 mM to 5 mM) on fully differentiated 3T3-L1 cells (mature adipocytes). Results: We demonstrated that NAC treatment was not toxic to mature adipocytes. Only 5mM NAC inhibited reactive oxygen species production. 5 mM NAC treatment resulted in a 60% decrease in cellular triglycerides content and inhibited 70% cholesterol accumulation.  We also determined the mRNA and protein expression levels of Peroxisome Proliferator-Activated Receptor g as well as, mRNA levels of lipid protein Perilipin in NAC treated adipocytes; we observed that 5mM NAC treatment caused nearly 30% decrease in the expression of these parameters. Conclusion: These results suggest that NAC could avoid lipid accumulation in mature adipocytes; the antioxidant NAC could be beneficial in obesity treatment.

JNK- and IκB-dependent pathways regulate MCP-1 but not adiponectin release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro

2008 ◽  
Vol 294 (5) ◽  
pp. E898-E909 ◽  
Author(s):  
Kazuto Takahashi ◽  
Shinya Yamaguchi ◽  
Tatsuhiro Shimoyama ◽  
Hiroyuki Seki ◽  
Kaoru Miyokawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diglycidyl Ether ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Parallel Increase ◽  
Tnf Α ◽  
Jnk Inhibitors ◽  
Factor Α

Obese conditions increase the expression of adipocytokine monocyte chemoattractant protein-1 (MCP-1) in adipose tissue as well as MCP-1 plasma levels. To investigate the mechanism behind increased MCP-1, we used a model in which 3T3-L1 adipocytes were artificially hypertrophied by preloading with palmitate in vitro. As observed in obesity, under our model conditions, palmitate-preloaded cells showed significantly increased oxidative stress and increased MCP-1 expression relative to control cells. This increased MCP-1 expression was enhanced by adding exogenous tumor necrosis factor-α (TNF-α; 17.8-fold vs. control cells, P < 0.01) rather than interleukin-1β (IL-1β; 2.6-fold vs. control cells, P < 0.01). However, endogenous TNF-α and IL-1β release was not affected in hypertrophied cells, suggesting that these endogenous cytokines do not mediate hypertrophy-induced increase in MCP-1. MCP-1 secretion from hypertrophied cells was significantly decreased by treatment with antioxidant N-acetyl-cysteine, JNK inhibitors SP600125 and JIP-1 peptide, and IκB phosphorylation inhibitors BAY 11-7085 and BMS-345541 ( P < 0.01). MCP-1 secretion was not affected by peroxisome proliferator-activated receptor-γ (PPARγ) antagonists assayed. Adiponectin, another adipocytokine studied in parallel, also showed increased release in hypertrophy relative to control cells. But in contrast to MCP-1, adiponectin release was significantly suppressed by both exogenous TNF-α and IL-1β as well as by PPARγ antagonists bisphenol A diglycidyl ether and T0070907 ( P < 0.01). JNK inhibitors and IκB phosphorylation inhibitors showed no significant effect on adiponectin. We conclude that adipocyte hypertrophy through palmitate loading causes oxidative stress, which in turn increases MCP-1 expression and secretion through JNK and IκB signaling. In contrast, the parallel increase in adiponectin expression appears to be related to the PPARγ ligand properties of palmitate.

scholarly journals Endogenous Generation and Signaling Actions of Omega-3 Fatty Acid Electrophilic Derivatives

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Chiara Cipollina
Keyword(s):  
Oxidative Stress ◽  
Ex Vivo ◽  
Antioxidant Response ◽  
Peroxisome Proliferator ◽  
Unsaturated Ketone ◽  
Omega 3 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Derivatives Of ◽  
And Oxidative Stress

Dietary omega-3 polyunsaturated fatty acids (PUFAs) are beneficial for a number of conditions ranging from cardiovascular disease to chronic airways disorders, neurodegeneration, and cancer. Growing evidence has shown that bioactive oxygenated derivatives are responsible for transducing these salutary effects. Electrophilic oxo-derivatives of omega-3 PUFAs represent a class of oxidized derivatives that can be generated via enzymatic and nonenzymatic pathways. Inflammation and oxidative stress favor the formation of these signaling species to promote the resolution of inflammation within a fine autoregulatory loop. Endogenous generation of electrophilic oxo-derivatives of omega-3 PUFAs has been observed inin vitroandex vivohuman models and dietary supplementation of omega-3 PUFAs has been reported to increase their formation. Due to the presence of anα,β-unsaturated ketone moiety, these compounds covalently and reversibly react with nucleophilic residues on target proteins triggering the activation of cytoprotective pathways, including the Nrf2 antioxidant response, the heat shock response, and the peroxisome proliferator activated receptorγ(PPARγ) and suppressing the NF-κB proinflammatory pathway. The endogenous nature of electrophilic oxo-derivatives of omega-3 PUFAs combined with their ability to simultaneously activate multiple cytoprotective pathways has made these compounds attractive for the development of new therapies for the treatment of chronic disorders and acute events characterized by inflammation and oxidative stress.

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