Peroxisome Proliferator-Activated Receptor α (PPARα) Activators, Bezafibrate and Wy-14,643, Increase Uncoupling Protein-3 mRNA Levels without Modifying the Mitochondrial Membrane Potential in Primary Culture of Rat Preadipocytes

2000 ◽  
Vol 380 (2) ◽  
pp. 353-359 ◽  
Author(s):  
Àgatha Cabrero ◽  
Marta Alegret ◽  
Rosa Sánchez ◽  
Tomás Adzet ◽  
Juan C. Laguna ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Primary Culture ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Uncoupling Protein 3

Grape Seed Proanthocyanidins Protect N2a Cells against Ischemic Injury via Endoplasmic Reticulum Stress and Mitochondrial-associated Pathways

2019 ◽  
Vol 18 (4) ◽  
pp. 334-341 ◽  
Author(s):  
Kun Fu ◽  
Liqiang Chen ◽  
Lifeng Miao ◽  
Yan Guo ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Cell Viability ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Grape Seed ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Grape Seed Proanthocyanidins ◽  
N2a Cells ◽  
Caspase 12

Background/Objective: Grape seed proanthocyanidins (GSPs) are a group of polyphenolic bioflavonoids, which possess a variety of biological functions and pharmacological properties. We studied the neuroprotective effects of GSP against oxygen-glucose deprivation/reoxygenation (OGD/R) injury and the potential mechanisms in mouse neuroblastoma N2a cells. Methods: OGD/R was conducted in N2a cells. Cell viability was evaluated by CCK-8 and LDH release assay. Apoptosis was assessed by TUNEL staining and flow cytometry. Protein levels of cleaved caspase-3, Bax and Bcl-2 were detected by Western blotting. CHOP, GRP78 and caspase-12 mRNA levels were assessed by real-time PCR. JC-1 dying was used to detect mitochondrial membrane potential. ROS levels, activities of endogenous antioxidant enzymes and ATP production were examined to evaluate mitochondrial function. Results: GSP increased cell viability after OGD/R injury in a dose-dependent manner. Furthermore, GSP inhibited cell apoptosis, reduced the mRNA levels of CHOP, GRP78 and caspase-12 (ER stressassociated genes), restored mitochondrial membrane potential and ATP generation, improved activities of endogenous anti-oxidant ability (T-AOC, GXH-Px, and SOD), and decreased ROS level. Conclusion: Our findings suggest that GSP can protect N2a cells from OGD/R insult. The mechanism of anti-apoptotic effects of GSP may involve attenuating ER stress and mitochondrial dysfunction.

scholarly journals Two Subpopulations of Human Monocytes That Differ by Mitochondrial Membrane Potential

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 153
Author(s):  
Nikita G. Nikiforov ◽  
Anastasia Ryabova ◽  
Marina V. Kubekina ◽  
Igor D. Romanishkin ◽  
Kirill A. Trofimov ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Primary Culture ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Intima Media Thickness ◽  
Mtdna Mutations ◽  
Proinflammatory Activity

Atherosclerosis is associated with a chronic local inflammatory process in the arterial wall. Our previous studies have demonstrated the altered proinflammatory activity of circulating monocytes in patients with atherosclerosis. Moreover, atherosclerosis progression and monocyte proinflammatory activity were associated with mitochondrial DNA (mtDNA) mutations in circulating monocytes. The role of mitochondria in the immune system cells is currently well recognized. They can act as immunomodulators by releasing molecules associated with bacterial infection. We hypothesized that atherosclerosis can be associated with changes in the mitochondrial function of circulating monocytes. To test this hypothesis, we performed live staining of the mitochondria of CD14+ monocytes from healthy donors and atherosclerosis patients with MitoTracker Orange CMTMRos dye, which is sensitive to mitochondrial membrane potential. The intensity of such staining reflects mitochondrial functional activity. We found that parts of monocytes in the primary culture were characterized by low MitoTracker staining (MitoTracker-low monocytes). Such cells were morphologically similar to cells with normal staining and able to metabolize 5-aminolevulinic acid and accumulate the heme precursor protoporphyrin IX (PplX), indicative of partially preserved mitochondrial function. We assessed the proportion of MitoTracker-low monocytes in the primary culture for each study subject and compared the results with other parameters, such as monocyte ability to lipopolysaccharide (LPS)-induced proinflammatory activation and the intima-media thickness of carotid arteries. We found that the proportion of MitoTracker-low monocytes was associated with the presence of atherosclerotic plaques. An increased number of such monocytes in the primary culture was associated with a reduced proinflammatory activation ability of cells. The obtained results indicate the presence of circulating monocytes with mitochondrial dysfunction and the association of such cells with chronic inflammation and atherosclerosis development.

scholarly journals Peroxisome Proliferator-Activated Receptor α (PPARα) Potentiates, whereas PPARγ Attenuates, Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3266-3276 ◽  
Author(s):  
Kim Ravnskjaer ◽  
Michael Boergesen ◽  
Blanca Rubi ◽  
Jan K. Larsen ◽  
Tina Nielsen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Mitochondrial Membrane ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Stimulated Insulin Secretion

Abstract Fatty acids (FAs) are known to be important regulators of insulin secretion from pancreatic β-cells. FA-coenzyme A esters have been shown to directly stimulate the secretion process, whereas long-term exposure of β-cells to FAs compromises glucose-stimulated insulin secretion (GSIS) by mechanisms unknown to date. It has been speculated that some of these long-term effects are mediated by members of the peroxisome proliferator-activated receptor (PPAR) family via an induction of uncoupling protein-2 (UCP2). In this study we show that adenoviral coexpression of PPARα and retinoid X receptor α (RXRα) in INS-1E β-cells synergistically and in a dose- and ligand-dependent manner increases the expression of known PPARα target genes and enhances FA uptake and β-oxidation. In contrast, ectopic expression of PPARγ/RXRα increases FA uptake and deposition as triacylglycerides. Although the expression of PPARα/RXRα leads to the induction of UCP2 mRNA and protein, this is not accompanied by reduced hyperpolarization of the mitochondrial membrane, indicating that under these conditions, increased UCP2 expression is insufficient for dissipation of the mitochondrial proton gradient. Importantly, whereas expression of PPARγ/RXRα attenuates GSIS, the expression of PPARα/RXRα potentiates GSIS in rat islets and INS-1E cells without affecting the mitochondrial membrane potential. These results show a strong subtype specificity of the two PPAR subtypes α and γ on lipid partitioning and insulin secretion when systematically compared in a β-cell context.

scholarly journals Uncoupling Protein 2 Drives Myocardial Dysfunction in Murine Models of Septic Shock

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Rong Tang ◽  
Ping-ping Qi ◽  
Yan-song Liu ◽  
Liu Jia ◽  
Rui-jin Liu ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Cardiac Dysfunction ◽  
Mitochondrial Membrane ◽  
Viral Vector ◽  
Therapeutic Potential ◽  
Uncoupling Protein ◽  
Myocardial Dysfunction ◽  
Multiorgan Failure ◽  
Uncoupling Protein 2

Cardiac dysfunction is a major component of sepsis-induced multiorgan failure in critical care units. Uncoupling protein 2 (UCP2) involves immune response, regulation of oxidative stress, and maintenance of mitochondrial membrane potential as well as energy production. However, whether and how UCP2 plays roles in the development of septic cardiac dysfunction are largely unknown. Here, intraperitoneal injection of LPS significantly activated UCP2 expression accompanied by a significant decrease of cardiac function and caused a significantly lower survival rate in mice. Of note, knockdown of UCP2 through a cardiotropic adenoassociated viral vector carrying a short hairpin RNA (shRNA) specifically targeting the UCP2 evoked resistance to LPS-triggered septic cardiac dysfunction and lethality in vivo. Moreover, UCP2 deficiency ameliorated the reduced levels of intracellular ATP in the LPS-challenged heart tissues and preserved mitochondrial membrane potential loss in primary adult mouse cardiomyocytes in LPS-challenged animals. Mechanistically, we confirmed that the inhibition of UCP2 promoted autophagy in response to LPS, as shown by an increase in LC3II and a decrease in p62. At last, the autophagy inhibitor 3-MA abolished UCP2 knockdown-afforded cardioprotective effects. Those results indicate that UCP2 drives septic cardiac dysfunction and that the targeted induction of UCP2-mediated autophagy may have important therapeutic potential.

Uncoupling protein 3 transcription is regulated by peroxisome proliferator‐activated receptor α in the adult rodent heart

2001 ◽  
Vol 15 (3) ◽  
pp. 833-845 ◽  
Author(s):  
MARTIN E. YOUNG ◽  
SARITA PATIL ◽  
JUN YING ◽  
CHRISTOPHE DEPRE ◽  
HARLEEN SINGH AHUJA ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Uncoupling Protein 3

Uncoupling Protein 3 and Peroxisome Proliferator-Activated Receptor γ2 Contribute to Obesity and Diabetes in Palauans

2001 ◽  
Vol 281 (3) ◽  
pp. 772-778 ◽  
Author(s):  
Yoshiko Yanagisawa ◽  
Kyoko Hasegawa ◽  
Gregory J. Dever ◽  
Caleb Tyn.O. Otto ◽  
Mitsuru Sakuma ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Obesity And Diabetes ◽  
Uncoupling Protein 3

scholarly journals Leptin Rapidly Induces the Expression of Metabolic and Myokine Genes in C2C12 Muscle Cells to Regulate Nutrient Partition and Oxidation

2015 ◽  
Vol 35 (1) ◽  
pp. 92-103 ◽  
Author(s):  
Yuriy Nozhenko ◽  
Ana M. Rodríguez ◽  
Andreu Palou
Keyword(s):  
Time Course ◽  
Leptin Receptor ◽  
Uncoupling Protein ◽  
Muscle Cells ◽  
Pyruvate Dehydrogenase Kinase ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels

Background: Skeletal muscle can experience pronounced metabolic adaptations in response to extrinsic stimuli, and expresses leptin receptor (OB-Rb). We aimed to further the understanding of leptin effects on muscle cells, by studying the expression of key energy metabolism genes in C2C12 myotubes. Methods: We performed a dose-time-dependent study with physiological concentrations of leptin: 5, 10 and 50ng/ml, for 0, 30', 3h, 6h, 12h and 24h, also monitoring time-course changes in non-treated cells. mRNA levels were analyzed by RT-qPCR and peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) protein levels by western blot. Results: The most significant effects were observed with 50ng/ml leptin. In the short-term (30' and/or 3h), leptin significantly induced the expression of PGC1α, muscle carnitine palmitoyl transferase 1 (mCPT1), uncoupling protein 3 (UCP3), OB-Rb, Insulin receptor (InsR) and interleukins 6 and 15 (IL6, IL15). There was a decrease in mRNA levels of pyruvate dehydrogenase kinase 4 (PDK4) and mCPT1 in the long-term (24h). PGC1α protein levels were increased (24h). Conclusion: Leptin rapidly induces the expression of genes important for its own response and the control of metabolic fuels, with the rapid responses of the genes encoding the master regulator PGC1α, mCPT1, UCP3, PDK4 and the signaling secretory molecule IL6 particularly interesting.

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