scholarly journals Possible Involvement of Mitochondrial Dysfunction and Oxidative Stress in a Cellular Model of NAFLD Progression Induced by Benzo[a]pyrene/Ethanol CoExposure

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Simon Bucher ◽  
Dounia Le Guillou ◽  
Julien Allard ◽  
Grégory Pinon ◽  
Karima Begriche ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Respiration ◽  
Mitochondrial Respiratory Chain ◽  
Ros Generation ◽  
Nonalcoholic Fatty Liver ◽  
Aryl Hydrocarbon ◽  
Heparg Cells ◽  
Mitochondrial Respiratory Chain Activity ◽  
Respiratory Chain Activity

Exposure to xenobiotics could favor the transition of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis in obese patients. Recently, we showed in different models of NAFL that benzo[a]pyrene (B[a]P) and ethanol coexposure induced a steatohepatitis-like state. One model was HepaRG cells incubated with stearate and oleate for 2 weeks. In the present study, we wished to determine in this model whether mitochondrial dysfunction and reactive oxygen species (ROS) overproduction could be involved in the occurrence of this steatohepatitis-like state. CRISPR/Cas9-modified cells were also used to specify the role of aryl hydrocarbon receptor (AhR), which is potently activated by B[a]P. Thus, nonsteatotic and steatotic HepaRG cells were treated with B[a]P, ethanol, or both molecules for 2 weeks. B[a]P/ethanol coexposure reduced mitochondrial respiratory chain activity, mitochondrial respiration, and mitochondrial DNA levels and induced ROS overproduction in steatotic HepaRG cells. These deleterious effects were less marked or absent in steatotic cells treated with B[a]P alone or ethanol alone and in nonsteatotic cells treated with B[a]P/ethanol. Our study also disclosed that B[a]P/ethanol-induced impairment of mitochondrial respiration was dependent on AhR activation. Hence, mitochondrial dysfunction and ROS generation could explain the occurrence of a steatohepatitis-like state in steatotic HepaRG cells exposed to B[a]P and ethanol.

scholarly journals Ovarian Tumor Mitochondria Exhibit Abnormal Phenotypes and Blunted Associations with Biobehavioral Factors

2021 ◽  
Author(s):  
Snehal Bindra ◽  
Marlon McGill ◽  
Marina Triplett ◽  
Anisha Tyagi ◽  
Premal Thaker ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Respiratory Chain ◽  
Ovarian Tissue ◽  
Mitochondrial Respiratory Chain ◽  
Ovarian Tumors ◽  
Mitochondrial Content ◽  
Benign Tissue ◽  
Mitochondrial Respiratory Chain Activity ◽  
Respiratory Chain Activity ◽  
And Function

Abstract Tumor cells exhibit mitochondrial alterations and are also influenced by biobehavioral processes, but the intersection of biobehavioral factors and tumor mitochondria remains unexplored. Here we examined multiple biochemical and molecular markers of mitochondrial content and function in benign and cancerous ovarian tissue in parallel with exploratory analyses of biobehavioral factors. First, analysis of a publicly-available database (n=1,435) showed that gene expression of specific mitochondrial proteins in ovarian tumors is associated with survival. Quantifying multiple biochemical and molecular markers of mitochondrial content and function in 51 benign and 128 high-grade epithelial ovarian tumors revealed that compared to benign tissue, tumors exhibit 3.3-8.4-fold higher mitochondrial content and respiratory chain enzymatic activities (P<0.001) but similar mitochondrial DNA levels (-3.1%), documenting abnormal mitochondrial phenotypes in tumors. Mitochondrial respiratory chain activity was also associated with interleukin-6 (IL-6) levels in ascites. In benign tissue, negative biobehavioral factors were inversely correlated with mitochondrial content and respiratory chain activities, whereas positive biobehavioral factors tended to be positively correlated with mitochondrial measures, although effect sizes were small to medium (r=-0.43 to 0.47). In contrast, serous tumors showed less pronounced biobehavioral-mitochondrial correlations. These results document abnormal mitochondrial functional phenotypes in ovarian tumors and warrant further research on the link between biobehavioral factors and mitochondria in cancer.

Mitochondrial respiratory chain activity in an animal model of mania induced by ouabain

2011 ◽  
Vol 23 (3) ◽  
pp. 106-111 ◽  
Author(s):  
Tiago P. Freitas ◽  
Gislaine T. Rezin ◽  
Daiane B. Fraga ◽  
Morgana Moretti ◽  
Julia S. Vieira ◽  
...  
Keyword(s):  
Animal Model ◽  
Prefrontal Cortex ◽  
Respiratory Chain ◽  
Rebound Effect ◽  
Mitochondrial Respiratory Chain ◽  
Face Validity ◽  
Mitochondrial Respiratory Chain Activity ◽  
Respiratory Chain Activity ◽  
The Brain ◽  
Mitochondrial Respiratory

Objectives: Bipolar disorder (BD) is a mental illness associated with higher rates of suicide. The present study aims to investigate the brain mitochondrial respiratory chain activity in an animal model of mania induced by ouabain.Methods: Adult male Wistar rats received a single intracerebroventricular administration of ouabain (10−3 and 10−2 M) or vehicle. Locomotor activity was measured using the open field test. Mitochondrial respiratory chain activity was measured in the brain of rats 1 h and 7 days after ouabain administration.Results: Our results showed that spontaneous locomotion was increased 1 h and 7 days after ouabain administration. Complexes I, III and IV activities were increased in the prefrontal cortex, hippocampus and striatum immediately after the administration of ouabain, at the concentration of 10−3 and 10−2 M. Moreover, complex II activity was increased only in the prefrontal cortex at the concentration of 10−2 M. On the other hand, no significant alterations were observed in complex I activity 7 days after ouabain administration. However, an increase in complexes II, III and IV activities was observed only in the prefrontal cortex at the concentration of 10−2 M.Conclusion: Our findings suggest an increase in the activities of mitochondrial respiratory chain in this model of mania. A possible explanation is that these findings occur as a rebound effect trying to compensate for a decrease of ATP deprivation in BD. The present findings suggest that this model may present good face validity and a limitation in construct validity.

scholarly journals miR-210 in Exosomes Derived from Macrophages under High Glucose Promotes Mouse Diabetic Obesity Pathogenesis by Suppressing NDUFA4 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Feng Tian ◽  
Ping Tang ◽  
Zhilian Sun ◽  
Ruifen Zhang ◽  
Danhua Zhu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
High Glucose ◽  
Mitochondrial Respiratory Chain ◽  
Raw264.7 Cells ◽  
Luciferase Reporter ◽  
Complex Activity ◽  
Adipose Tissue Macrophages ◽  
Mitochondrial Respiratory Chain Activity ◽  
Respiratory Chain Activity

Objective. Type 2 diabetes mellitus (T2DM) is featured by insulin resistance and lipid metabolism dysregulation. A large number of miRNAs were identified in exosomes derived from adipose tissue macrophages associated with T2DM pathogenesis, but its pathogenic roles remain unknown. This study is aimed at investigating the function of miR-210 in diabetic obesity. Methods. Exosomes from mouse macrophage RAW264.7 cells were characterized by electron microscopy, combined with biomarker expression by western blot. Expression of miR-210 was determined by quantitative RT-PCR. Glucose uptake was measured by a fluorometric method, and the mitochondrial respiratory chain activity was evaluated by ELISA. The target gene of miR-210 was validated by dual-luciferase reporter and pull-down assays. A mouse obese diabetic model was established by a high-fat diet and streptozocin treatment. Results. miR-210 was highly expressed in exosomes derived from high glucose-induced macrophage RAW264.7 cells. Macrophage-derived exosomes impaired glucose uptake and mitochondrial CIV complex activity and suppressed NADH dehydrogenase ubiquinone 1 alpha subcomplex 4 (NDUFA4) expression in 3T3-L1 adipocytes. miR-210 directly bind with mRNA sequences of NDUFA4 gene. Inhibition of miR-210 mitigated the effects of macrophage-derived exosomes on the glucose uptake and complex IV (CIV) activity in 3T3-L1 adipocytes, and NDUFA4 overexpression offset the inhibition of glucose uptake and CIV activity by macrophage-derived exosomes. Furthermore, mice with miR-210 knockout showed greatly repressed diabetic obesity development. Conclusion. miR-210 derived from adipose tissue macrophages promotes mouse obese diabetes pathogenesis by regulating glucose uptake and mitochondrial CIV activity through targeting NDUFA4 gene expression.

The nuclear receptor peroxisome proliferator-activated receptor-γ promotes oligodendrocyte differentiation through mechanisms involving mitochondria and oscillatory Ca2+ waves

2013 ◽  
Vol 394 (12) ◽  
pp. 1607-1614 ◽  
Author(s):  
Antonietta Bernardo ◽  
Roberta De Simone ◽  
Chiara De Nuccio ◽  
Sergio Visentin ◽  
Luisa Minghetti
Keyword(s):  
Nuclear Receptor ◽  
Neurological Diseases ◽  
Mitochondrial Respiratory Chain ◽  
Peroxisome Proliferator ◽  
Neuroprotective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Environmental Signals ◽  
Ppar Γ ◽  
Mitochondrial Respiratory Chain Activity ◽  
Respiratory Chain Activity

Abstract Peroxisome proliferator-activated receptor-γ (PPAR-γ) is one of the most studied nuclear receptor since its identification as a target to treat metabolic and neurological diseases. In addition to exerting anti-inflammatory and neuroprotective effects, PPAR-γ agonists, such as the insulin-sensitizing drug pioglitazone, promote the differentiation of oligodendrocytes (OLs), the myelin-forming cells of the central nervous system (CNS). In addition, PPAR-γ agonists increase OL mitochondrial respiratory chain activity and OL’s ability to respond to environmental signals with oscillatory Ca2+ waves. Both OL maturation and oscillatory Ca2+ waves are prevented by the mitochondrial inhibitor rotenone and restored by PPAR-γ agonists, suggesting that PPAR-γ promotes myelination through mechanisms involving mitochondria.

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