scholarly journals Mediating Roles of PPARs in the Effects of Environmental Chemicals on Sex Steroids

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Qiansheng Huang ◽  
Qionghua Chen
Keyword(s):  
Reproductive System ◽  
Sex Steroids ◽  
Environmental Pollutants ◽  
Environmental Chemicals ◽  
Peroxisome Proliferator ◽  
Altered Expression ◽  
In Silico Docking ◽  
Peroxisome Proliferator Activated Receptors ◽  
Peroxisome Proliferator Response Element ◽  
And Function

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that are widely involved in various physiological functions. They are widely expressed through the reproductive system. Their roles in the metabolism and function of sex steroids and thus the etiology of reproductive disorders receive great concern. Various kinds of exogenous chemicals, especially environmental pollutants, exert their adverse impact on the reproductive system through disturbing the PPAR signaling pathway. Chemicals could bind to PPARs and modulate the transcription of downstream genes containing PPRE (peroxisome proliferator response element). This will lead to altered expression of genes related to metabolism of sex steroids and thus the abnormal physiological function of sex steroids. In this review, various kinds of environmental ligands are summarized and discussed. Their interactions with three types of PPARs are classified by various data from transcript profiles, PPRE reporter in cell line, in silico docking, and gene silencing. The review will contribute to the understanding of the roles of PPARs in the reproductive toxicology of environmental chemicals.

scholarly journals Environmental pollutants-dependent molecular pathways and carcinogenesis

Biodiscovery ◽  
2019 ◽  
Vol 22 ◽  
Author(s):  
Myriam El Helou ◽  
Pascale A. Cohen ◽  
Mona Diab-Assaf ◽  
Sandra Ghayad
Keyword(s):  
Gene Expression ◽  
Environmental Pollutants ◽  
Environmental Chemicals ◽  
Gene Repair ◽  
Hormone Production ◽  
Aryl Hydrocarbon ◽  
Repair Mechanisms ◽  
Cellular Signal ◽  
And Function ◽  
G Protein Coupled

Exposure to environmental pollutants can modulate many biological and molecular processes such as gene expression, gene repair mechanisms, hormone production and function and inflammation, resulting in adverse effects on human health including the occurrence and development of different types of cancer. Carcinogenesis is a complex and long process, taking place in multiple stages and is affected by multiple factors. Some environmental molecules are genotoxic, able to damage the DNA or to induce mutations and changes in gene expression acting as initiators of carcinogenesis. Other molecules called xenoestrogens can promote carcinogenesis by their mitogenic effects by possessing estrogenic-like activities and consequently acting as endocrine disruptors causing multiple alterations in cellular signal transduction pathways. In this review, we focus on recent research on environmental chemicals-driven molecular functions in human cancers. For this purpose, we will be discussing the case of two receptors in mediating environmental pollutants effects: the established nuclear receptor, the Aryl hydrocarbon receptor (AhR) and the emerging membrane receptor, G-protein coupled estrogen receptor 1 (GPER1).

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 Peroxisome Proliferator-Activated Receptors in Female Reproduction and Fertility

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Maurizio Vitti ◽  
Giovanna Di Emidio ◽  
Michela Di Carlo ◽  
Gaspare Carta ◽  
Andrea Antonosante ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Environmental Pollutants ◽  
Peroxisome Proliferator ◽  
Female Reproduction ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Exogenous Agents ◽  
Peroxisome Proliferator Activated Receptors

Reproductive functions may be altered by the exposure to a multitude of endogenous and exogenous agents, drug or environmental pollutants, which are known to affect gene transcription through the peroxisome proliferator-activated receptors (PPARs) activation. PPARs act as ligand activated transcription factors and regulate metabolic processes such as lipid and glucose metabolism, energy homeostasis, inflammation, and cell proliferation and differentiation. All PPARs isotypes are expressed along the hypothalamic-pituitary-gonadal axis and are strictly involved in reproductive functions. Since female fertility and energy metabolism are tightly interconnected, the research on female infertility points towards the exploration of potential PPARs activating/antagonizing compounds, mainly belonging to the class of thiazolidinediones (TZDs) and fibrates, as useful agents for the maintenance of metabolic homeostasis in women with ovarian dysfunctions. In the present review, we discuss the recent evidence about PPARs expression in the hypothalamic-pituitary-gonadal axis and their involvement in female reproduction. Finally, the therapeutic potential of their manipulation through several drugs is also discussed.

Peroxisome Proliferator-activated Receptors: Stuctures and Function

1996 ◽  
Vol 804 (1 Peroxisomes) ◽  
pp. 252-265 ◽  
Author(s):  
JONATHAN D. TUGWOOD ◽  
THOMAS C. ALDRIDGE ◽  
KEVIN G. LAMBE ◽  
NEIL MACDONALD ◽  
NICOLA J. WOODYATT
Keyword(s):  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Function

scholarly journals Regulation of ENaC-Mediated Sodium Reabsorption by Peroxisome Proliferator-Activated Receptors

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Tengis S. Pavlov ◽  
John D. Imig ◽  
Alexander Staruschenko
Keyword(s):  
Collecting Duct ◽  
Fluid Retention ◽  
Sodium Absorption ◽  
Sodium Reabsorption ◽  
Receptor Subtype ◽  
Peroxisome Proliferator ◽  
Potential Contribution ◽  
Rate Limiting Step ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Function

Peroxisome proliferator-activated receptors (PPARs) are members of a steroid hormone receptor superfamily that responds to changes in lipid and glucose homeostasis. Peroxisomal proliferator-activated receptor subtypeγ(PPARγ) has received much attention as the target for antidiabetic drugs, as well as its role in responding to endogenous compounds such as prostaglandinJ2. However, thiazolidinediones (TZDs), the synthetic agonists of the PPARγare tightly associated with fluid retention and edema, as potentially serious side effects. The epithelial sodium channel (ENaC) represents the rate limiting step for sodium absorption in the renal collecting duct. Consequently, ENaC is a central effector impacting systemic blood volume and pressure. The role of PPARγagonists on ENaC activity remains controversial. While PPARγagonists were shown to stimulate ENaC-mediated renal salt absorption, probably via Serum- and Glucocorticoid-Regulated Kinase 1 (SGK1), other studies reported that PPARγagonist-induced fluid retention is independent of ENaC activity. The current paper provides new insights into the control and function of ENaC and ENaC-mediated sodium transport as well as several other epithelial channels/transporters by PPARs and particularly PPARγ. The potential contribution of arachidonic acid (AA) metabolites in PPAR-dependent mechanisms is also discussed.

scholarly journals Role of the Arylhydrocarbon Receptor (AhR) in the Pathology of Asthma and COPD

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Takahito Chiba ◽  
Junichi Chihara ◽  
Masutaka Furue
Keyword(s):  
Inflammatory Diseases ◽  
Environmental Pollutants ◽  
Chronic Obstructive ◽  
Peroxisome Proliferator ◽  
Environmental Toxicants ◽  
Obstructive Pulmonary Disease ◽  
Mucin Production ◽  
Arylhydrocarbon Receptor ◽  
Peroxisome Proliferator Activated Receptors

The dioxins and dioxin-like compounds in cigarette smoke and environmental pollutants modulate immunological responses. These environmental toxicants are known to cause lung cancer but have also recently been implicated in allergic and inflammatory diseases such as bronchitis, asthma, and chronic obstructive pulmonary disease (COPD). In a novel pathway of this response, the activation of a nuclear receptor, arylhydrocarbon receptor (AhR), mediates the effects of these toxins through the arachidonic acid cascade, cell differentiation, cell-cell adhesion interactions, cytokine expression, and mucin production that are implicated in the pathogenesis and exacerbation of asthma/COPD. We have previously reported that human bronchial epithelial cells express AhR, and AhR activation induces mucin production through reactive oxygen species. This review discusses the role of AhR in asthma and COPD, focusing in particular on inflammatory and resident cells in the lung. We describe the important impact that AhR activation may have on the inflammation phase in the pathology of asthma and COPD. In addition, crosstalk of AhR signaling with other ligand-activated transcription factors such as peroxisome proliferator-activated receptors (PPARs) has been well documented.

scholarly journals Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

PPAR Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-18 ◽  
Author(s):  
Oxana Yu. Kytikova ◽  
Juliy M. Perelman ◽  
Tatyana P. Novgorodtseva ◽  
Yulia K. Denisenko ◽  
Viktor P. Kolosov ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Treatment Effectiveness ◽  
Therapeutic Agents ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Signaling Mechanisms ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Function ◽  
Ppar Ligands ◽  
Potential Use

The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferator-activated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.

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