scholarly journals Peroxisome Proliferator-Activated Receptors (PPARs) and Oxidative Stress in Physiological Conditions and in Cancer

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1734
Author(s):  
Giuliana Muzio ◽  
Giuseppina Barrera ◽  
Stefania Pizzimenti
Keyword(s):  
Oxidative Stress ◽  
Cellular Response ◽  
Expression Patterns ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Orphan Nuclear Receptors ◽  
Antioxidant Genes ◽  
Physiological Conditions ◽  
Cell Functions ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor superfamily. Originally described as “orphan nuclear receptors”, they can bind both natural and synthetic ligands acting as agonists or antagonists. In humans three subtypes, PPARα, β/δ, γ, are encoded by different genes, show tissue-specific expression patterns, and contribute to the regulation of lipid and carbohydrate metabolisms, of different cell functions, including proliferation, death, differentiation, and of processes, as inflammation, angiogenesis, immune response. The PPAR ability in increasing the expression of various antioxidant genes and decreasing the synthesis of pro-inflammatory mediators, makes them be considered among the most important regulators of the cellular response to oxidative stress conditions. Based on the multiplicity of physiological effects, PPAR involvement in cancer development and progression has attracted great scientific interest with the aim to describe changes occurring in their expression in cancer cells, and to investigate the correlation with some characteristics of cancer phenotype, including increased proliferation, decreased susceptibility to apoptosis, malignancy degree and onset of resistance to anticancer drugs. This review focuses on mechanisms underlying the antioxidant and anti-inflammatory properties of PPARs in physiological conditions, and on the reported beneficial effects of PPAR activation in cancer.

scholarly journals PPARs and Myocardial Infarction

2020 ◽  
Vol 21 (24) ◽  
pp. 9436
Author(s):  
Kay-Dietrich Wagner ◽  
Nicole Wagner
Keyword(s):  
Myocardial Infarction ◽  
Therapeutic Potential ◽  
Pathological Condition ◽  
Expression Patterns ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Specific Expression ◽  
Ppar Agonists ◽  
Cell Type Specific Expression ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family. They are ligand-activated transcription factors and exist in three different isoforms, PPARα (NR1C1), PPARβ/δ (NR1C2), and PPARγ (NR1C3). PPARs regulate a variety of functions, including glucose and lipid homeostasis, inflammation, and development. They exhibit tissue and cell type-specific expression patterns and functions. Besides the established notion of the therapeutic potential of PPAR agonists for the treatment of glucose and lipid disorders, more recent data propose specific PPAR ligands as potential therapies for cardiovascular diseases. In this review, we focus on the knowledge of PPAR function in myocardial infarction, a severe pathological condition for which therapeutic use of PPAR modulation has been suggested.

scholarly journals Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

scholarly journals Peroxisome Proliferator-Activated Receptors (PPARs) Activation as Therapeutic Targets in Skin Inflammation

2020 ◽  
Vol 4 (2) ◽  
pp. 9
Author(s):  
Akihiro Aioi
Keyword(s):  
Skin Diseases ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Cell Types ◽  
Immune Dysregulation ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Barrier Dysfunction ◽  
Cytokine Network ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are fatty acid activated transcription factors that belong to the nuclear hormone receptor family. They are initially known as transcriptional regulators of lipid and glucose metabolism, although further evidence has also been accumulated for other functions. Due to the nature of all PPAR isotypes which are expressed and exert effects by regulating the functions of cell types residing and infiltrating in the skin, PPARs represent a major research target for the understanding and treatment of many skin diseases. Atopic dermatitis (AD) is a chronic and relapsing disease characterized by skin barrier dysfunction and immune dysregulation. Skin barrier disturbance is one of the exacerbation factors of AD, due to facile penetration of molecules such as antigens. From the aspect of immune dysregulation, innate and acquired immunity including cell proliferation, cell differentiation, and cytokine network are involved in the pathogenesis. In this review, the role of PPAR in AD and the possibility of its agonist for the treatment of AD are discussed.

scholarly journals Hepatic Lipid Catabolism via PPARα-Lysosomal Crosstalk

2020 ◽  
Vol 21 (7) ◽  
pp. 2391 ◽  
Author(s):  
Rohit A. Sinha ◽  
Sangam Rajak ◽  
Brijesh K. Singh ◽  
Paul M. Yen
Keyword(s):  
Energy Metabolism ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Reciprocal Regulation ◽  
Alcoholic Fatty Liver ◽  
Lysosomal Activity ◽  
Hepatic Lipid ◽  
Peroxisome Proliferator Activated Receptors ◽  
Key Aspects ◽  
Alcoholic Fatty Liver Disease

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which belong to the nuclear hormone receptor superfamily. They regulate key aspects of energy metabolism within cells. Recently, PPARα has been implicated in the regulation of autophagy-lysosomal function, which plays a key role in cellular energy metabolism. PPARα transcriptionally upregulates several genes involved in the autophagy-lysosomal degradative pathway that participates in lipolysis of triglycerides within the hepatocytes. Interestingly, a reciprocal regulation of PPARα nuclear action by autophagy-lysosomal activity also exists with implications in lipid metabolism. This review succinctly discusses the unique relationship between PPARα nuclear action and lysosomal activity and explores its impact on hepatic lipid homeostasis under pathological conditions such as non-alcoholic fatty liver disease (NAFLD).

scholarly journals Effects of peroxisome proliferator activated receptors (PPAR)-γ and -α agonists on cochlear protection from oxidative stress

PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0188596 ◽  
Author(s):  
Marijana Sekulic-Jablanovic ◽  
Vesna Petkovic ◽  
Matthew B. Wright ◽  
Krystsina Kucharava ◽  
Nathan Huerzeler ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals The Role of Peroxisome Proliferator-Activated Receptors in Pulmonary Vascular Disease

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
Rachel E. Nisbet ◽  
Roy L. Sutliff ◽  
C. Michael Hart
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Disease ◽  
Vascular Dysfunction ◽  
Treatment Strategies ◽  
Underlying Disease ◽  
Nuclear Hormone Receptor ◽  
Pulmonary Vascular Disease ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Function

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily that regulate diverse physiological processes ranging from lipogenesis to inflammation. Recent evidence has established potential roles of PPARs in both systemic and pulmonary vascular disease and function. Existing treatment strategies for pulmonary hypertension, the most common manifestation of pulmonary vascular disease, are limited by an incomplete understanding of the underlying disease pathogenesis and lack of efficacy indicating an urgent need for new approaches to treat this disorder. Derangements in pulmonary endothelial-derived mediators and endothelial dysfunction have been shown to play a pivotal role in pulmonary hypertension pathogenesis. Therefore, the following review will focus on selected mediators implicated in pulmonary vascular dysfunction and evidence that PPARs, in particular PPARγ, participate in their regulation and may provide a potential novel therapeutic target for the treatment of pulmonary hypertension.

scholarly journals Activation of Peroxisome Proliferator-Activated Receptorγby Rosiglitazone Inhibits Lipopolysaccharide-Induced Release of High Mobility Group Box 1

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Jung Seok Hwang ◽  
Eun Sil Kang ◽  
Sun Ah Ham ◽  
Taesik Yoo ◽  
Hanna Lee ◽  
...  
Keyword(s):  
Cellular Response ◽  
Survival Rates ◽  
High Mobility ◽  
Inhibitory Effect ◽  
High Mobility Group ◽  
Raw 264.7 Cells ◽  
Signal Molecules ◽  
Peroxisome Proliferator ◽  
Treatment And Prevention ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are shown to modulate the pathological status of sepsis by regulating the release of high mobility group box 1 (HMGB1), a well-known late proinflammatory mediator of sepsis. Ligand-activated PPARs markedly inhibited lipopolysaccharide- (LPS) induced release of HMGB1 in RAW 264.7 cells. Among the ligands of PPAR, the effect of rosiglitazone, a specific ligand for PPARγ, was superior in the inhibition of HMGB1 release induced by LPS. This effect was observed in cells that received rosiglitazone before LPS or after LPS treatment, indicating that rosiglitazone is effective in both treatment and prevention. Ablation of PPARγwith small interfering RNA or GW9662-mediated inhibition of PPARγabolished the effect of rosiglitazone on HMGB1 release. Furthermore, the overexpression of PPARγmarkedly potentiated the inhibitory effect of rosiglitazone on HMGB1 release. In addition, rosiglitazone inhibited LPS-induced expression of Toll-like receptor 4 signal molecules, suggesting a possible mechanism by which rosiglitazone modulates HMGB1 release. Notably, the administration of rosiglitazone to mice improved survival rates in an LPS-induced animal model of endotoxemia, where reduced levels of circulating HMGB1 were demonstrated. Taken together, these results suggest that PPARs play an important role in the cellular response to inflammation by inhibiting HMGB1 release.

scholarly journals The Role of BRG1 in Antioxidant and Redox Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Shilong You ◽  
Ying Zhang ◽  
Jiaqi Xu ◽  
Hao Qian ◽  
Shaojun Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chromatin Remodeling ◽  
Redox Homeostasis ◽  
Redox Signaling ◽  
Normal Functioning ◽  
Antioxidant Genes ◽  
Cellular Processes ◽  
Cell Functions ◽  
Chromatin Remodeling Complex

Redox homeostasis is regulated by critical molecules that modulate antioxidant and redox signaling (ARS) within the cell. Imbalances among these molecules can lead to oxidative stress and damage to cell functions, causing a variety of diseases. Brahma-related gene 1 (BRG1), also known as SMARCA4, is the central ATPase catalytic subunit of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, which plays a core role in DNA replication, repair, recombination, and transcriptional regulation. Numerous recent studies show that BRG1 is involved in the regulation of various cellular processes associated with ARS. BRG1, as a major factor in chromatin remodeling, is essential for the repair of oxidative stress-induced DNA damage and the activation of antioxidant genes under oxidative stress. Consequently, a comprehensive understanding of the roles of BRG1 in redox homeostasis is crucial to understand the normal functioning as well as pathological mechanisms. In this review, we summarized and discussed the role of BRG1 in the regulation of ARS.

scholarly journals Peroxisome Proliferator-Activated Receptors and Shock State

2006 ◽  
Vol 6 ◽  
pp. 1770-1782 ◽  
Author(s):  
Emanuela Esposito ◽  
Salvatore Cuzzocrea ◽  
Rosaria Meli
Keyword(s):  
Transcription Factors ◽  
Energy Homeostasis ◽  
Hormone Receptors ◽  
Inflammatory Responses ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Shock State ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors ◽  
Inflammatory Molecules

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid, and thyroid hormone receptors. Three isotypes of PPARs have been identified: alpha, beta/delta, and gamma, encoded by different genes and distributed in various tissues. PPARs are implicated in the control of inflammatory responses and in energy homeostasis and, thus, can be defined as metabolic and anti-inflammatory transcription factors. They exert anti-inflammatory effects by inhibiting the induction of proinflammatory cytokines, adhesion molecules, and extracellular matrix proteins, or by stimulating the production of anti-inflammatory molecules. Moreover, PPARs modulate the proliferation, differentiation, and survival of immune cells. This review presents the current state of knowledge regarding the involvement of PPARs in the control of inflammatory response, and their potential therapeutic applications in several types of shock, as well as hemorrhagic, septic, and nonseptic shock.

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