scholarly journals PPAR-γ agonist rosiglitazone ameliorates peritoneal deterioration in peritoneal dialysis rats with LPS-induced peritonitis through up-regulation of AQP-1 and ZO-1

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Yunfang Zhang ◽  
Junxia Feng ◽  
Qi Wang ◽  
Shili Zhao ◽  
Jiaqi Xu ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Therapeutic Potential ◽  
Cell Monolayer ◽  
Mesothelial Cell ◽  
Structure And Function ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
And Function ◽  
Lps Treatment

Peritonitis is still a major cause of the death in peritoneal dialysis (PD) patients despite the significant decline of the peritonitis rates in recent years. The present study is designed to evaluate the therapeutic potential of peroxisome proliferator-activated receptor-γ agonist, rosiglitazone, on the structure and function of the peritoneum in a PD rat accompanied with peritonitis induced by lipopolysaccharide (LPS). Our data showed that the peritoneal membrane in the LPS-only group showed increased peritoneal thickness, vessel density, and hypercellularity compared with the PD-only group. Rosiglitazone administration significantly inhibited increase of the three indicators in PD rats with LPS treatment. In line with this, rosiglitazone improved function of the peritoneum in LPS-induced PD rats receiving rosiglitazone, which was reflected by decreased D/P urea and D/P albumin. Mechanistically, rosiglitazone-mediated improvements in the damaged structure and function of the peritoneum in PD rats with LPS treatment were associated with reduced inflammation and preserving mesothelial cell monolayer resulted from up-regulation of AQP-1 and ZO-1. Our findings thus suggest that peroxisome proliferator-activated receptor γ (PPAR-γ) activation might be a reasonable strategy to prevent and ameliorate peritoneal deterioration in PD patients, especially with peritonitis.

scholarly journals Immunometabolic modulation of retinal inflammation by CD36 ligand

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Katia Mellal ◽  
Samy Omri ◽  
Mukandila Mulumba ◽  
Houda Tahiri ◽  
Carl Fortin ◽  
...  
Keyword(s):  
Mononuclear Phagocytes ◽  
Inflammasome Activation ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pyrin Domain ◽  
Ppar Γ ◽  
Injury Characteristic ◽  
And Function ◽  
Cluster Of Differentiation

Abstract In subretinal inflammation, activated mononuclear phagocytes (MP) play a key role in the progression of retinopathies. Little is known about the mechanism involved in the loss of photoreceptors leading to vision impairment. Studying retinal damage induced by photo-oxidative stress, we observed that cluster of differentiation 36 (CD36)-deficient mice featured less subretinal MP accumulation and attenuated photoreceptor degeneration. Moreover, treatment with a CD36-selective azapeptide ligand (MPE-001) reduced subretinal activated MP accumulation in wild type mice and preserved photoreceptor layers and function as assessed by electroretinography in a CD36-dependent manner. The azapeptide modulated the transcriptome of subretinal activated MP by reducing pro-inflammatory markers. In isolated MP, MPE-001 induced dissociation of the CD36-Toll-like receptor 2 (TLR2) oligomeric complex, decreasing nuclear factor-kappa B (NF-κB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. In addition, MPE-001 caused an aerobic metabolic shift in activated MP, involving peroxisome proliferator-activated receptor-γ (PPAR-γ) activation, which in turn mitigated inflammation. Accordingly, PPAR-γ inhibition blocked the cytoprotective effect of MPE-001 on photoreceptor apoptosis elicited by activated MP. By altering activated MP metabolism, MPE-001 decreased immune responses to alleviate subsequent inflammation-dependent neuronal injury characteristic of various vision-threatening retinal disorders.

The Role of Peroxisome Proliferator–Activated Receptor γ in Colon Cancer and Inflammatory Bowel Disease

2003 ◽  
Vol 127 (9) ◽  
pp. 1121-1123
Author(s):  
Arthur W. Bull
Keyword(s):  
Inflammatory Bowel Disease ◽  
Colon Cancer ◽  
Bowel Disease ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Inflammatory Bowel

Abstract Objective.—Review the role and therapeutic potential of peroxisome proliferator–activated receptor (PPAR) γ in colonic disorders. Data Sources.—Recent peer-reviewed scientific literature focusing on PPAR γ in the colon. Study Selection.—Research reports using animal models, cultured cell lines, and clinical material were examined for content related to the role of PPAR γ in normal colon cell function, colon cancer, and inflammatory bowel disease. Issues concerned with potential therapeutic use were also considered. Data Synthesis.—Key points pertaining to PPAR function and involvement in colon pathology were extracted and noted. Potential compromises to therapeutic utility are identified. Conclusions.—The emerging important role of PPAR γ in normal tissue homeostasis and pathologic outcomes suggests this receptor is a good candidate as a drug target. Several potential problems with this approach will require further investigation prior to widespread recommendations for modulation of PPAR as an efficacious therapy for cancer, chemoprevention of colon cancer, or treatment of inflammatory bowel disease. The widespread use of PPAR γ ligands for management of type 2 diabetes (such as the glitazone class of drugs including rosiglitazone and pioglitazone) may provide a fortuitous assessment of the efficacy of long-term PPAR modulation.

scholarly journals Smooth Muscle-Targeted Overexpression of Peroxisome Proliferator Activated Receptor-γ Disrupts Vascular Wall Structure and Function

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0139756 ◽  
Author(s):  
Jennifer M. Kleinhenz ◽  
Tamara C. Murphy ◽  
Anastassia P. Pokutta-Paskaleva ◽  
Rudolph L. Gleason ◽  
Alicia N. Lyle ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Wall ◽  
Structure And Function ◽  
Wall Structure ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
And Function

scholarly journals Peroxisome Proliferator-Activated Receptors (PPAR)γ Agonists as Master Modulators of Tumor Tissue

2018 ◽  
Vol 19 (11) ◽  
pp. 3540 ◽  
Author(s):  
Daniel Heudobler ◽  
Michael Rechenmacher ◽  
Florian Lüke ◽  
Martin Vogelhuber ◽  
Tobias Pukrop ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Therapeutic Potential ◽  
Molecular Genetic ◽  
Cancer Control ◽  
Metastatic Tumor ◽  
Therapy Resistance ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Communicative Behavior ◽  
Ppar Γ

In most clinical trials, thiazolidinediones do not show any relevant anti-cancer activity when used as mono-therapy. Clinical inefficacy contrasts ambiguous pre-clinical data either favoring anti-tumor activity or tumor promotion. However, if thiazolidinediones are combined with additional regulatory active drugs, so-called ‘master modulators’ of tumors, i.e., transcriptional modulators, metronomic low-dose chemotherapy, epigenetically modifying agents, protein binding pro-anakoinotic drugs, such as COX-2 inhibitors, IMiDs, etc., the results indicate clinically relevant communicative reprogramming of tumor tissues, i.e., anakoinosis, meaning ‘communication’ in ancient Greek. The concerted activity of master modulators may multifaceted diversify palliative care or even induce continuous complete remission in refractory metastatic tumor disease and hematologic neoplasia by establishing novel communicative behavior of tumor tissue, the hosting organ, and organism. Re-modulation of gene expression, for example, the up-regulation of tumor suppressor genes, may recover differentiation, apoptosis competence, and leads to cancer control—in contrast to an immediate, ‘poisoning’ with maximal tolerable doses of targeted/cytotoxic therapies. The key for uncovering the therapeutic potential of Peroxisome proliferator-activated receptor γ (PPARγ) agonists is selecting the appropriate combination of master modulators for inducing anakoinosis: Now, anakoinosis is trend setting by establishing a novel therapeutic pillar while overcoming classic obstacles of targeted therapies, such as therapy resistance and (molecular-)genetic tumor heterogeneity.

scholarly journals The current stage of neuroprotection: development of mitochondria-targeted approaches

2020 ◽  
pp. 4-19
Author(s):  
Ф.М. Шакова ◽  
Ю.И. Кирова ◽  
Г.А. Романова
Keyword(s):  
Ischemic Stroke ◽  
Structure And Function ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Transcriptional Coactivator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pharmacological Modulation ◽  
Promising Strategy ◽  
And Function ◽  
Current Stage

Обзор посвящен рассмотрению современных подходов к фармакологической модуляции структурно-функционального состояния митохондриального аппарата нейронов как перспективной стратегии терапии ишемического инсульта головного мозга, составляющего по современным оценкам до 85% всех случаев острого нарушения мозгового кровообращения. В обзоре проведен анализ классических представлений о нейропротекции как терапии, направленной на блокирование ключевых патогенетических звеньев «ишемического каскада», в контексте современного понимания приоритетной роли коррекции митохондриальной дисфункции в ограничении механизмов повреждения при церебральной ишемии. Обсуждаются возможности применения препаратов плейотропного нейропротекторного действия, реализующих митохондриально-направленные защитные эффекты через модуляцию активности транскрипционного коактиватора PGC-1α (peroxisome proliferator-activated receptor-1γ coactivator-1α), контролирующего процессы биогенеза митохондрий, ангиогенеза, ферментативное звено антиоксидантной системы. The review addresses modern approaches to pharmacological modulation of structure and function of the neuronal mitochondrial apparatus. This is a promising strategy for therapy of ischemic stroke, which accounts for up to 85% of all cases of acute cerebrovascular disease. The review analyzes classical concepts of neuroprotection as a therapy aimed at blocking key pathogenetic components of the “ischemic cascade”. These concepts are based on current ideas about the importance of correcting mitochondrial dysfunction for alleviation of damage in cerebral ischemia. The authors discussed possibilities of using pleiotropic neuroprotectors that implement mitochondrial-targeted protective effects by modulating the activity of transcriptional coactivator, peroxisome proliferator-activated receptor-1γ coactivator-1α (PGC-1α), which controls mitochondrial biogenesis, angiogenesis, and the enzymatic antioxidant system.

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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