scholarly journals Long-term outcomes of monascin – a novel dual peroxisome proliferator-activated receptor γ/nuclear factor-erythroid 2 related factor-2 agonist in experimental intracerebral hemorrhage

2020 ◽  
Vol 13 ◽  
pp. 175628642092108
Author(s):  
Pengcheng Fu ◽  
Jiachen Liu ◽  
Qinqin Bai ◽  
Xingang Sun ◽  
Zhenjia Yao ◽  
...  
Keyword(s):  
Brain Injury ◽  
Iron Overload ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Nuclear Factor ◽  
Long Term Outcomes ◽  
Hematoma Volume ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Background: Hematoma is the chief culprit in brain injury following intracranial cerebral hemorrhage (ICH). Noninvasive hematoma clearance could be an option to prevent and alleviate early brain injury after ICH. Peroxisome proliferator-activated receptor γ (PPAR-γ) and nuclear factor-erythroid 2 related factor-2 (Nrf2) facilitate removal of hematoma in ICH. Monascin acts as the natural Nrf2 activator with PPAR-γ agonist, and the long-term effects of monascin following ICH have not been elucidated. Methods: ICH in rats was induced by stereotactic, intrastriatal injection of type IV collagenase. Monascin was administered twice daily by gastric perfusion for 14 days after ICH induction. Long-term neurological scores (T maze, Garcia scales, rotor rod test, and Morris water maze), hematoma volume, as well as iron overload around hematoma and brain atrophy were evaluated at 7, 14, and 28 days after ICH. Results: The results showed that monascin improved long-term neurological deficits, spatial memory performance, learning ability, and brain shrinkage after ICH. Monascin also reduced hematoma volume at 7 days and iron content at 7 and 14 days after ICH. Conclusion: PPAR γ and Nrf2 play a crucial role in hematoma clearance after ICH in rat. As a dual agonist of PPAR γ and Nrf2, monascin improved long-term outcomes by facilitating hematoma clearance, and by attenuating iron overload and brain atrophy after experimental ICH.

scholarly journals Curcumin Attenuates Gentamicin-Induced Kidney Mitochondrial Alterations: Possible Role of a Mitochondrial Biogenesis Mechanism

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Mario Negrette-Guzmán ◽  
Wylly Ramsés García-Niño ◽  
Edilia Tapia ◽  
Cecilia Zazueta ◽  
Sara Huerta-Yepez ◽  
...  
Keyword(s):  
Curcuma Longa ◽  
Nuclear Accumulation ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Nuclear Factor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Alterations ◽  
Mitochondrial Functions

It has been shown that curcumin (CUR), a polyphenol derived fromCurcuma longa, exerts a protective effect against gentamicin- (GM-) induced nephrotoxicity in rats, associated with a preservation of the antioxidant status. Although mitochondrial dysfunction is a hallmark in the GM-induced renal injury, the role of CUR in mitochondrial protection has not been studied. In this work, LLC-PK1 cells were preincubated 24 h with CUR and then coincubated 48 h with CUR and 8 mM GM. Treatment with CUR attenuated GM-induced drop in cell viability and led to an increase in nuclear factor (erythroid-2)-related factor 2 (Nrf2) nuclear accumulation and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) cell expression attenuating GM-induced losses in these proteins.In vivo, Wistar rats were injected subcutaneously with GM (75 mg/Kg/12 h) during 7 days to develop kidney mitochondrial alterations. CUR (400 mg/Kg/day) was administered orally 5 days before and during the GM exposure. The GM-induced mitochondrial alterations in ultrastructure and bioenergetics as well as decrease in activities of respiratory complexes I and IV and induction of calcium-dependent permeability transition were mostly attenuated by CUR. Protection of CUR against GM-induced nephrotoxicity could be in part mediated by maintenance of mitochondrial functions and biogenesis with some participation of the nuclear factor Nrf2.

scholarly journals Peroxisome Proliferator-Activated Receptor -β/δ, -γAgonists and Resveratrol Modulate Hypoxia Induced Changes in Nuclear Receptor Activators of Muscle Oxidative Metabolism

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Timothy R. H. Regnault ◽  
Lin Zhao ◽  
Jacky S. S. Chiu ◽  
Stephanie K. Gottheil ◽  
Allison Foran ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Oxidative Metabolism ◽  
Intrauterine Growth Restriction ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Hypoxia Adaptation ◽  
Induced Changes ◽  
Ppar Pathway

PPAR-α, PPAR-β, and PPAR-γ, and RXR in conjunction with PGC-1α and SIRT1, activate oxidative metabolism genes determining insulin sensitivity. In utero, hypoxia is commonly observed in Intrauterine Growth Restriction (IUGR), and reduced insulin sensitivity is often observed in these infants as adults. We sought to investigate how changes in oxygen tension might directly impact muscle PPAR regulation of oxidative genes. Following eight days in culture at 1% oxygen, C2C12muscle myoblasts displayed a reduction of PGC-1α, PPAR-α, and RXR-α mRNA, as well as CPT-1b and UCP-2 mRNA. SIRT1 and PGC-1α protein was reduced, and PPAR-γ protein increased. The addition of a PPAR-β agonist (L165,041) for the final 24 hours of 1% treatment resulted in increased levels of UCP-2 mRNA and protein whereas Rosiglitazone induced SIRT1, PGC-1α, RXR-α, PPAR-α, CPT-1b, and UCP-2 mRNA and SIRT1 protein. Under hypoxia, Resveratrol induced SIRT1, RXR-α, PPAR-α mRNA, and PPAR-γ and UCP-2 protein. These findings demonstrate that hypoxia alters the components of the PPAR pathway involved in muscle fatty acid oxidative gene transcription and translation. These results have implications for understanding selective hypoxia adaptation and how it might impact long-term muscle oxidative metabolism and insulin sensitivity.

scholarly journals NRF2 and PPAR-γ Pathways in Oligodendrocyte Progenitors: Focus on ROS Protection, Mitochondrial Biogenesis and Promotion of Cell Differentiation

2020 ◽  
Vol 21 (19) ◽  
pp. 7216
Author(s):  
Chiara De Nuccio ◽  
Antonietta Bernardo ◽  
Carmen Troiano ◽  
Maria Stefania Brignone ◽  
Mario Falchi ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Mitochondrial Biogenesis ◽  
Dimethyl Fumarate ◽  
Demyelinating Diseases ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Necrosis Factor Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Reactions ◽  
Ppar Γ

An adequate protection from oxidative and inflammatory reactions, together with the promotion of oligodendrocyte progenitor (OP) differentiation, is needed to recover from myelin damage in demyelinating diseases. Mitochondria are targets of inflammatory and oxidative insults and are essential in oligodendrocyte differentiation. It is known that nuclear factor-erythroid 2-related factor/antioxidant responsive element (NRF2/ARE) and peroxisome proliferator-activated receptor gamma/PPAR-γ response element (PPAR-γ/PPRE) pathways control inflammation and overcome mitochondrial impairment. In this study, we analyzed the effects of activators of these pathways on mitochondrial features, protection from inflammatory/mitochondrial insults and cell differentiation in OP cultures, to depict the specificities and similarities of their actions. We used dimethyl-fumarate (DMF) and pioglitazone (pio) as agents activating NRF2 and PPAR-γ, respectively, and two synthetic hybrids acting differently on the NRF2/ARE pathway. Only DMF and compound 1 caused early effects on the mitochondria. Both DMF and pio induced mitochondrial biogenesis but different antioxidant repertoires. Moreover, pio induced OP differentiation more efficiently than DMF. Finally, DMF, pio and compound 1 protected from tumor necrosis factor-alpha (TNF-α) insult, with pio showing faster kinetics of action and compound 1 a higher activity than DMF. In conclusion, NRF2 and PPAR-γ by inducing partially overlapping pathways accomplish complementary functions aimed at the preservation of mitochondrial function, the defense against oxidative stress and the promotion of OP differentiation.

Regulation of dectin-1–mediated dendritic cell activation by peroxisome proliferator–activated receptor-gamma ligand troglitazone

Blood ◽  
2011 ◽  
Vol 117 (13) ◽  
pp. 3569-3574 ◽  
Author(s):  
Grethe Kock ◽  
Anita Bringmann ◽  
Stefanie Andrea Erika Held ◽  
Solveig Daecke ◽  
Annkristin Heine ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Nuclear Factor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Mitogen Activated Protein

Abstract Dectin-1 is the major receptor for fungal β-glucans. The activation of Dectin-1 leads to the up-regulation of surface molecules on dendritic cells (DCs) and cytokine secretion. Furthermore, Dectin-1 is important for the recruitment of leukocytes and the production of inflammatory mediators. Peroxisome proliferator–activated receptor-γ (PPAR-γ) and its ligands, cyclopentenone prostaglandins or thiazolidinediones, have modulatory effects on B-cell, T-cell, and DC function. In the present study, we analyzed the effects of troglitazone (TGZ), a high-affinity synthetic PPAR-γ ligand, on the Dectin-1–mediated activation of monocyte-derived human DCs. Dectin-1–mediated activation of DCs was inhibited by TGZ, as shown by down-regulation of costimulatory molecules and reduced secretion of cytokines and chemokines involved in T-lymphocyte activation. Furthermore, TGZ inhibited the T-cell–stimulatory capacity of DCs. These effects were not due to a diminished expression of Dectin-1 or to a reduced phosphorylation of spleen tyrosine kinase; they were mediated by the inhibition of downstream signaling molecules such as mitogen-activated protein kinases and nuclear factor-κB. Furthermore, curdlan-mediated accumulation of caspase recruitment domain 9 (CARD9) in the cytosol was inhibited by TGZ. Our data demonstrate that the PPAR-γ ligand TGZ inhibits Dectin-1–mediated activation by interfering with CARD9, mitogen-activated protein kinase, and nuclear factor-κB signaling pathways. This confirms their important role as negative-feedback regulators of potentially harmful inflammatory responses.

scholarly journals (–)-Epicatechin Reduces the Blood Pressure of Young Borderline Hypertensive Rats During the Post-Treatment Period

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 96 ◽  
Author(s):  
Michal Kluknavsky ◽  
Peter Balis ◽  
Martin Skratek ◽  
Jan Manka ◽  
Iveta Bernatova
Keyword(s):  
Blood Pressure ◽  
Young Male ◽  
Post Treatment ◽  
No Production ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Hypertensive Rats ◽  
Gene Expressions ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

This study investigated the effects of (–)-epicatechin (Epi) in young male borderline hypertensive rats (BHR) during two weeks of treatment (Epi group, 100 mg/kg/day p.o.) and two weeks post treatment (PE group). Epi reduced blood pressure (BP), which persisted for two weeks post treatment. This was associated with delayed reduction of anxiety-like behaviour. Epi significantly increased nitric oxide synthase (NOS) activities in the aorta and left heart ventricle (LHV) vs. the age-matched controls without affecting the brainstem and frontal neocortex. Furthermore, Epi significantly reduced the superoxide production in the aorta and relative content of iron-containing compounds in blood. Two weeks post treatment, the NOS activities and superoxide productions in the heart and aorta did not differ from the age-matched controls. The gene expressions of the NOSs (nNOS, iNOS, eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor-γ (PPAR-γ) remained unaltered in the aorta and LHV of the Epi and PE groups. In conclusion, while Epi-induced a decrease of the rats’ BP persisted for two weeks post treatment, continuous Epi treatments seem to be necessary for maintaining elevated NO production as well as redox balance in the heart and aorta without changes in the NOSs, Nrf2, and PPAR-γ gene expressions.

GLUTATHIONE TRANSFERASES

2005 ◽  
Vol 45 (1) ◽  
pp. 51-88 ◽  
Author(s):  
John D. Hayes ◽  
Jack U. Flanagan ◽  
Ian R. Jowsey
Keyword(s):  
Oxidative Stress ◽  
Antitumor Agents ◽  
Glutathione Transferase ◽  
Degradation Products ◽  
Nuclear Factor Κb ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Nuclear Factor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Increased Risk

This review describes the three mammalian glutathione transferase (GST) families, namely cytosolic, mitochondrial, and microsomal GST, the latter now designated MAPEG. Besides detoxifying electrophilic xenobiotics, such as chemical carcinogens, environmental pollutants, and antitumor agents, these transferases inactivate endogenous α,β-unsaturated aldehydes, quinones, epoxides, and hydroperoxides formed as secondary metabolites during oxidative stress. These enzymes are also intimately involved in the biosynthesis of leukotrienes, prostaglandins, testosterone, and progesterone, as well as the degradation of tyrosine. Among their substrates, GSTs conjugate the signaling molecules 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and 4-hydroxynonenal with glutathione, and consequently they antagonize expression of genes trans-activated by the peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). Through metabolism of 15d-PGJ2, GST may enhance gene expression driven by nuclear factor-κB (NF-κB). Cytosolic human GST exhibit genetic polymorphisms and this variation can increase susceptibility to carcinogenesis and inflammatory disease. Polymorphisms in human MAPEG are associated with alterations in lung function and increased risk of myocardial infarction and stroke. Targeted disruption of murine genes has demonstrated that cytosolic GST isoenzymes are broadly cytoprotective, whereas MAPEG proteins have proinflammatory activities. Furthermore, knockout of mouse GSTA4 and GSTZ1 leads to overexpression of transferases in the Alpha, Mu, and Pi classes, an observation suggesting they are part of an adaptive mechanism that responds to endogenous chemical cues such as 4-hydroxynonenal and tyrosine degradation products. Consistent with this hypothesis, the promoters of cytosolic GST and MAPEG genes contain antioxidant response elements through which they are transcriptionally activated during exposure to Michael reaction acceptors and oxidative stress.

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