scholarly journals Effects of PPARγLigands on Leukemia

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Yoko Tabe ◽  
Marina Konopleva ◽  
Michael Andreeff ◽  
Akimichi Ohsaka
Keyword(s):  
Hematological Malignancies ◽  
Therapeutic Agents ◽  
Retinoic Acid Receptors ◽  
Peroxisome Proliferator ◽  
Cellular Functions ◽  
Growth And Survival ◽  
Hematopoietic Malignancies ◽  
Retinoid Metabolism ◽  
Natural Ligands ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) and retinoic acid receptors (RARs), members of the nuclear receptor superfamily, are transcription factors that regulate a variety of important cellular functions. PPARs form heterodimers retinoid X receptor (RXR), an obligate heterodimeric partner for other nuclear receptors. Several novel links between retinoid metabolism and PPAR responses have been identified, and activation of PPAR/RXR expression has been shown to increase response to retinoids. PPARγhas emerged as a key regulator of cell growth and survival, whose activity is modulated by a number of synthetic and natural ligands. While clinical trials in cancer patients with thiazolidinediones (TZD) have been disappointing, novel structurally different PPARγligands, including triterpenoids, have entered clinical arena as therapeutic agents for epithelial and hematopoietic malignancies. Here we shall review the antitumor advances of PPARγ, alone and in combination with RARαligands in control of cell proliferation, differentiation, and apoptosis and their potential therapeutic applications in hematological malignancies.

scholarly journals Peroxisome Proliferator Activated Receptor Ligands as Regulators of Airway Inflammation and Remodelling in Chronic Lung Disease

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-12 ◽  
Author(s):  
Jane Elizabeth Ward ◽  
Xiahui Tan
Keyword(s):  
Lung Disease ◽  
Airway Inflammation ◽  
Inflammatory Cells ◽  
Peroxisome Proliferator ◽  
Cellular Functions ◽  
Mucus Production ◽  
Peroxisome Proliferator Activated Receptor ◽  
Chronic Lung Diseases ◽  
Peroxisome Proliferator Activated Receptors

Inflammation is a major component in the pathology of chronic lung diseases, including asthma. Anti-inflammatory treatment with corticosteroids is not effective in all patients. Thus, new therapeutic options are required to control diverse cellular functions that are currently not optimally targeted by these drugs in order to inhibit inflammation and its sequelae in lung disease. Peroxisome proliferator activated receptors (PPARs), originally characterised as regulators of lipid and glucose metabolism, offer marked potential in this respect. PPARs are expressed in both lung infiltrating and resident immune and inflammatory cells, as well as in resident and structural cells in the lungs, and play critical roles in the regulation of airway inflammation. In vitro, endogenous and synthetic ligands for PPARs regulate expression and release of proinflammatory cytokines and chemoattractants, and cell proliferation and survival. In murine models of allergen-induced inflammation, PPARαand PPARγligands reduce the influx of inflammatory cells, cytokine and mucus production, collagen deposition, and airways hyperresponsiveness. The activity profiles of PPAR ligands differ to corticosteroids, supporting the hypothesis that PPARs comprise additional therapeutic targets to mimimise the contribution of inflammation to airway remodelling and dysfunction.

scholarly journals Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators, and corepressors.

1997 ◽  
Vol 17 (4) ◽  
pp. 2166-2176 ◽  
Author(s):  
J DiRenzo ◽  
M Söderstrom ◽  
R Kurokawa ◽  
M H Ogliastro ◽  
M Ricote ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Nuclear Receptor ◽  
Target Genes ◽  
Direct Repeat ◽  
Retinoic Acid Receptors ◽  
Structural Motif ◽  
Peroxisome Proliferator ◽  
Response Elements ◽  
Peroxisome Proliferator Activated Receptors

As the obligate member of most nuclear receptor heterodimers, retinoid X receptors (RXRs) can potentially perform two functions: cooperative binding to hormone response elements and coordinate regulation of target genes by RXR ligands. In this paper we describe allosteric interactions between RXR and two heterodimeric partners, retinoic acid receptors (RARs) and peroxisome proliferator-activated receptors (PPARs); RARs and PPARs prevent and permit activation by RXR-specific ligands, respectively. By competing for dimerization with RXR on response elements consisting of direct-repeat half-sites spaced by 1 bp (DR1 elements), the relative abundance of RAR and PPAR determines whether the RXR signaling pathway will be functional. In contrast to RAR, which prevents the binding of RXR ligands and recruits the nuclear receptor corepressor N-CoR, PPAR permits the binding of SRC-1 in response to both RXR and PPAR ligands. Overexpression of SRC-1 markedly potentiates ligand-dependent transcription by PPARgamma, suggesting that SRC-1 serves as a coactivator in vivo. Remarkably, the ability of RAR to both block the binding of ligands to RXR and interact with corepressors requires the CoR box, a structural motif residing in the N-terminal region of the RAR ligand binding domain. Mutations in the CoR box convert RAR from a nonpermissive to a permissive partner of RXR signaling on DR1 elements. We suggest that the differential recruitment of coactivators and corepressors by RAR-RXR and PPAR-RXR heterodimers provides the basis for a transcriptional switch that may be important in controlling complex programs of gene expression, such as adipocyte differentiation.

scholarly journals Thyroid hormone receptors regulate adipogenesis and carcinogenesis via crosstalk signaling with peroxisome proliferator-activated receptors

2009 ◽  
Vol 44 (3) ◽  
pp. 143-154 ◽  
Author(s):  
Changxue Lu ◽  
Sheue-Yann Cheng
Keyword(s):  
Thyroid Hormone ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptors ◽  
Peroxisome Proliferator ◽  
Cellular Functions ◽  
Biological Impact ◽  
Hormone Response Elements ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) and thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily. They are ligand-dependent transcription factors that interact with their cognate hormone response elements in the promoters to regulate respective target gene expression to modulate cellular functions. While the transcription activity of each is regulated by their respective ligands, recent studies indicate that via multiple mechanisms PPARs and TRs crosstalk to affect diverse biological functions. Here, we review recent advances in the understanding of the molecular mechanisms and biological impact of crosstalk between these two important nuclear receptors, focusing on their roles in adipogenesis and carcinogenesis.

scholarly journals Nuclear receptor research in zebrafish

2017 ◽  
Vol 59 (1) ◽  
pp. R65-R76 ◽  
Author(s):  
Marcel J M Schaaf
Keyword(s):  
Animal Model ◽  
Retinoic Acid Receptors ◽  
Peroxisome Proliferator ◽  
Full Potential ◽  
Physiological Processes ◽  
Model Research ◽  
Wide Range ◽  
Peroxisome Proliferator Activated Receptors ◽  
Receptor Research ◽  
Almost All

Nuclear receptors (NRs) form a superfamily of transcription factors that can be activated by ligands and are involved in a wide range of physiological processes. NRs are well conserved between vertebrate species. The zebrafish, an increasingly popular animal model system, contains a total of 73 NR genes, and orthologues of almost all human NRs are present. In this review article, an overview is presented of NR research in which the zebrafish has been used as a model. Research is described on the three most studied zebrafish NRs: the estrogen receptors (ERs), retinoic acid receptors (RARs) and peroxisome proliferator-activated receptors (PPARs). The studies on these receptors illustrate the versatility of the zebrafish as a model for ecotoxicological, developmental and biomedical research. Although the use of the zebrafish in NR research is still relatively limited, it is expected that in the next decade the full potential of this animal model will be exploited.

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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