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.

Effect of vitamin D on isoprenaline-induced myocardial infarction in rats: possible role of peroxisome proliferator-activated receptor-γ

2017 ◽  
Vol 95 (6) ◽  
pp. 641-646 ◽  
Author(s):  
Ola Ahmed El-Gohary ◽  
Mona Maher Allam
Keyword(s):  
Myocardial Infarction ◽  
Vitamin D ◽  
Diglycidyl Ether ◽  
Peroxisome Proliferator ◽  
Oxidative Stress Biomarkers ◽  
Cardiac Damage ◽  
Necrosis Factor Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Infarct-like lesion induced by isoprenaline is a well-known model to study myocardial infarction (MI). Vitamin D has been shown to have anti-inflammatory and antioxidant effects. Recent studies highlighted cross talk between vitamin D and peroxisome proliferator-activated receptor gamma (PPAR-γ). The present study was designed to investigate the effect of pretreatment with vitamin D on the isoprenaline-induced infarct-like lesion in rats and the role of PPAR-γ as a novel mechanism in vitamin-D-mediated cardioprotective effect. Markers chosen to assess cardiac damage included serum level of creatine kinase (CK), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Cardiac contents of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH) were also assessed. Furthermore, ECG monitoring and measurement of injury extension were carried out. Isoprenaline increased the level of cardiac enzymes, as well as inflammatory and oxidative stress biomarkers. In addition, it produced ST-segment elevation. Pretreatment with vitamin D significantly improved previous parameters. The prior treatment with bisphenol A diglycidyl ether (BADGE), a PPAR-γ antagonist, significantly attenuated the protective effect of vitamin D. In conclusion, vitamin D can be demonstrated as a promising cardioprotective agent in MI and PPAR-γ significantly contributes toward vitamin-D-mediated protection.

scholarly journals Pentoxifylline Enhances Antioxidative Capability and Promotes Mitochondrial Biogenesis in D-Galactose-Induced Aging Mice by Increasing Nrf2 and PGC-1α through the cAMP-CREB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Yu Wang ◽  
Tianyun Zhang ◽  
Hui Zhao ◽  
Chunxiao Qi ◽  
Xiaoming Ji ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Mitochondrial Biogenesis ◽  
Phosphodiesterase Inhibitor ◽  
Adenosine Monophosphate ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Mitochondrial Ultrastructure ◽  
Peroxisome Proliferator Activated Receptor ◽  
Antioxidant Genes ◽  
Creb Pathway

Aging is a complex phenomenon associated with oxidative stress and mitochondrial dysfunction. The objective of this study was to investigate the potential ameliorative effects of the phosphodiesterase inhibitor pentoxifylline (PTX) on the aging process and its underlying mechanisms. We treated D-galactose- (D-gal-) induced aging mice with PTX and measured the changes in behavior, degree of oxidative damage, and mitochondrial ultrastructure and content as well as the expression of nuclear factor erythroid 2-related factor 2- (Nrf2-) mediated antioxidant genes and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha- (PGC-1α-) dependent mitochondrial biogenesis genes. The results demonstrated that PTX improved cognitive deficits, reduced oxidative damage, ameliorated abnormal mitochondrial ultrastructure, increased mitochondrial content and Nrf2 activation, and upregulated antioxidant and mitochondrial biogenesis gene expression in the hippocampus of wild-type aging mice. However, the above antiaging effects of PTX were obviously decreased in the brains of Nrf2-deficient D-gal-induced aging mice. Moreover, in hydrogen peroxide-treated SH-SY5Y cells, we found that cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and Nrf2/PGC-1α act in a linear way by CREB siRNA transfection. Thus, PTX administration improved the aging-related decline in brain function by enhancing antioxidative capability and promoting mitochondrial biogenesis, which might depend on increasing Nrf2 and PGC-1α by activating the cAMP-CREB pathway.

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.

scholarly journals Integrative genome-wide analysis of dopaminergic neuron-specific PARIS expression in Drosophila dissects recognition of multiple PPAR-γ associated gene regulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Volkan Yazar ◽  
Sung-Ung Kang ◽  
Shinwon Ha ◽  
Valina L. Dawson ◽  
Ted M. Dawson
Keyword(s):  
Mitochondrial Biogenesis ◽  
Target Genes ◽  
Affinity Purification ◽  
Transcriptome Profiling ◽  
Gene Clusters ◽  
Peroxisome Proliferator ◽  
Promoter Regions ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Genome Wide

AbstractThe transcriptional repressor called parkin interacting substrate (PARIS; ZNF746) was initially identified as a novel co-substrate of parkin and PINK1 that leads to Parkinson’s disease (PD) by disrupting mitochondrial biogenesis through peroxisome proliferator-activated receptor gamma (PPARγ) coactivator -1α (PGC-1α) suppression. Since its initial discovery, growing evidence has linked PARIS to defective mitochondrial biogenesis observed in PD pathogenesis. Yet, dopaminergic (DA) neuron-specific mechanistic underpinnings and genome-wide PARIS binding landscape has not been explored. We employed conditional translating ribosome affinity purification (TRAP) followed by RNA sequencing (TRAP-seq) for transcriptome profiling of DA neurons in transgenic Drosophila lines expressing human PARIS wild type (WT) or mutant (C571A). We also generated genome-wide maps of PARIS occupancy using ChIP-seq in human SH-SY5Y cells. The results demonstrated that PPARγ functions as a master regulator of PARIS-induced molecular changes at the transcriptome level, confirming that PARIS acts primarily on PGC-1α to lead to neurodegeneration in PD. Moreover, we identified that PARIS actively modulates expression of PPARγ target genes by physically binding to the promoter regions. Together, our work revealed how PARIS drives adverse effects on modulation of PPAR-γ associated gene clusters in DA neurons.

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.

Rhein attenuates lipopolysaccharide-primed inflammation through NF-κB inhibition in RAW264.7 cells: targeting the PPAR-γ signal pathway

2020 ◽  
Vol 98 (6) ◽  
pp. 357-365 ◽  
Author(s):  
Quan Wen ◽  
Jifei Miao ◽  
Ngaikeung Lau ◽  
Chaoying Zhang ◽  
Peng Ye ◽  
...  
Keyword(s):  
Inflammatory Process ◽  
Raw264.7 Cells ◽  
Inflammatory Factors ◽  
Peroxisome Proliferator ◽  
Inflammatory Factor ◽  
Necrosis Factor Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
Histone Deacetylase 3 ◽  
Ppar Γ ◽  
Anti Inflammatory

Inflammation is a common inducer of numerous severe diseases such as sepsis. The NF-κB signaling pathway plays a key role in the inflammatory process. Its activation promotes the release of pro-inflammatory mediators like inducible nitric oxide synthase and tumor necrosis factor alpha. Peroxisome proliferator-activated receptor gamma (PPAR-γ) inactivates nuclear factor kappa B (NF-κB) and subsequently attenuates inflammation. Rhein, an agent isolated from rhubarb, has been known to have anti-inflammatory effects. However, its influence on PPAR-γ remains largely unknown. In this study, an inflammation model was constructed by stimulating RAW264.7 cells with lipopolysaccharide. Rhein was used as a therapeutic agent, while rosiglitazone (PPAR-γ activator) and GW9662 (PPAR-γ inhibitor) were used as disrupters for in depth studies. The results demonstrated that rhein inhibits NF-κB activation and inflammatory factor release. However, GW9662 significantly reduced this effect, indicating that PPAR-γ is a critical mediator in the rhein-mediated anti-inflammatory process. Additionally, positive modulation of PPAR-γ expression and activity by rosiglitazone correspondingly influenced the effects of rhein on inflammatory factors and NF-κB expression. We also found that rhein could enhance PPAR-γ, NF-κB, and histone deacetylase 3 (HDAC3) binding. These results indicate that rhein exerts its anti-inflammation function by regulating the PPAR-γ–NF-κB–HDAC3 axis.

scholarly journals Curcumin promotes oligodendrocyte differentiation and their protection against TNF-α through the activation of the nuclear receptor PPAR-γ

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonietta Bernardo ◽  
Cristina Plumitallo ◽  
Chiara De Nuccio ◽  
Sergio Visentin ◽  
Luisa Minghetti
Keyword(s):  
Therapeutic Potential ◽  
Core Protein ◽  
Curcuma Longa ◽  
Demyelinating Diseases ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Conditions ◽  
Ppar Γ ◽  
Tnf Α ◽  
Anti Inflammatory

AbstractCurcumin is a compound found in the rhizome of Curcuma longa (turmeric) with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. The current study aims to assess the effects of this natural compound on oligodendrocyte progenitor (OP) differentiation, particularly in inflammatory conditions. We found that curcumin can promote the differentiation of OPs and to counteract the maturation arrest of OPs induced by TNF-α by a mechanism involving PPAR-γ (peroxisome proliferator activated receptor), a ligand-activated transcription factor with neuroprotective and anti-inflammatory capabilities. Furthermore, curcumin induces the phosphorylation of the protein kinase ERK1/2 known to regulate the transition from OPs to immature oligodendrocytes (OLs), by a mechanism only partially dependent on PPAR-γ. Curcumin is also able to raise the levels of the co-factor PGC1-α and of the cytochrome c oxidase core protein COX1, even when OPs are exposed to TNF-α, through a PPAR-γ-mediated mechanism, in line with the known ability of PPAR-γ to promote mitochondrial integrity and functions, which are crucial for OL differentiation to occur. Altogether, this study provides evidence for a further mechanism of action of curcumin besides its well-known anti-inflammatory properties and supports the suggested therapeutic potential of this nutraceutical in demyelinating diseases.

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