Estrogen-related receptor alpha interacts cooperatively with peroxisome proliferator-activated receptor-gamma coactivator-1alpha to regulate osteocalcin gene expression

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Haibin Wang ◽  
Junjian Wang
Keyword(s):  
Gene Expression ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha ◽  
Osteocalcin Gene ◽  
Estrogen Related Receptor

PerOXISOME PROLIFERATOR-ACTIVATED RECEPTOR-alpha-MEDIATED GENE EXPRESSION AND ADAPTATION TO FATTY ACID OVERLOAD IN ALCOHOLIC LIVER DISEASE

1998 ◽  
Vol 22 (3) ◽  
pp. 749-750 ◽  
Author(s):  
Nathan M. Bass ◽  
Rennaisance Appel ◽  
Edward J. Goetzl ◽  
Andrew J. Dannenberg ◽  
Amin A. Nanji
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha

scholarly journals Peroxisome proliferator-activated receptor alpha: role in rodent liver cancer and species differences

1999 ◽  
Vol 22 (1) ◽  
pp. 1-8 ◽  
Author(s):  
PR Holden ◽  
JD Tugwood
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Species Differences ◽  
Plasma Cholesterol ◽  
Specific Gene ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Apparent Lack ◽  
Receptor Alpha ◽  
Rats And Mice

Peroxisome proliferators (PPs) are chemicals of industrial and pharmaceutical importance that elicit liver carcinogenesis by a non-genotoxic mechanism. One of the intriguing properties of PPs is that the pleiotropic effects of these compounds (including increased DNA synthesis and peroxisome proliferation) are seen in rats and mice only, but not humans. It is important to determine the risks to humans of environmental and therapeutic exposure to these compounds by understanding the mechanisms of non-genotoxic hepatocarcinogenesis in rodents. To understand this apparent lack of human susceptibility, attention has focused on the peroxisome proliferator-activated receptor alpha (PPARalpha), which appears to mediate the effects of PPs in rodents. It is also known to mediate the hypolipidaemic effects that fibrate drugs exert on humans with elevated plasma cholesterol and triglyceride levels. Human PPARalphas share many functional characteristics with the rodent receptors, in that they can be transcriptionally activated by PPs and regulate specific gene expression. However, one key difference is that PPARalpha is less abundant in human than in rodent liver, which has led to the suggestion that species differences result from quantitative differences in gene expression. In this review we describe the effects of PPs and what is known of the molecular mechanisms of action and species differences with respect to rodents and man. Attention will be given to differences in the amounts of PPARalpha between species as well as the 'qualitative' aspects of PPARalpha-mediated gene regulation which might also explain the activation of some genes and not of others in human liver by PPs.

scholarly journals Fenofibrate Reduces the Severity of Neuroretinopathy in a Type 2 Model of Diabetes without Inducing Peroxisome Proliferator-Activated Receptor Alpha-Dependent Retinal Gene Expression

2020 ◽  
Vol 10 (1) ◽  
pp. 126
Author(s):  
Jennifer M. Enright ◽  
Sheng Zhang ◽  
Christina Thebeau ◽  
Emily Siebert ◽  
Alexander Jin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Elevated Serum ◽  
Oscillatory Potentials ◽  
Luciferase Reporter ◽  
Peroxisome Proliferator ◽  
Serum Triglycerides ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha ◽  
Peroxisome Proliferator Response Element

Fenofibrate slows the progression of clinical diabetic retinopathy (DR), but its mechanism of action in the retina remains unclear. Fenofibrate is a known agonist of peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor critical for regulating metabolism, inflammation and oxidative stress. Using a DR mouse model, db/db, we tested the hypothesis that fenofibrate slows early DR progression by activating PPARα in the retina. Relative to healthy littermates, six-month-old db/db mice exhibited elevated serum triglycerides and cholesterol, retinal gliosis, and electroretinography (ERG) changes including reduced b-wave amplitudes and delayed oscillatory potentials. These pathologic changes in the retina were improved by oral fenofibrate. However, fenofibrate did not induce PPARα target gene expression in whole retina or isolated Müller glia. The capacity of the retina to respond to PPARα was further tested by delivering the PPARα agonist GW590735 to the intraperitoneal or intravitreous space in mice carrying the peroxisome proliferator response element (PPRE)-luciferase reporter. We observed strong induction of the reporter in the liver, but no induction in the retina. In summary, fenofibrate treatment of db/db mice prevents the development of early DR but is not associated with induction of PPARα in the retina.

scholarly journals Induction of human CYP4A11 gene expression by fasting or peroxisome proliferator activated receptor alpha (PPARa) agonists in transgenic mice

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Üzen Savas ◽  
Daniel E. Machemer ◽  
Mei‐ H. Hsu ◽  
Pryce Gaynor ◽  
Jerome M. Lasker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha

scholarly journals Functional interference between estrogen-related receptor alpha and peroxisome proliferator-activated receptor alpha/9-cis-retinoic acid receptor alpha heterodimer complex in the nuclear receptor response element-1 of the medium chain acyl-coenzyme A dehydrogenase gene

2003 ◽  
Vol 31 (1) ◽  
pp. 47-60 ◽  
Author(s):  
K Maehara ◽  
T Hida ◽  
Y Abe ◽  
A Koga ◽  
K Ota ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Retinoic Acid Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha ◽  
Receptor Response ◽  
Chain Acyl ◽  
Acyl Coenzyme A ◽  
Estrogen Related Receptor

We undertook a study of molecular interference of nuclear orphan receptors. Nuclear receptor response element-1 (NRRE-1) from the human medium-chain acyl coenzyme A dehydrogenase (MCAD) gene promoter was shown to contain three hexamer elements (site 1 through 3) that are known to interact with a number of nuclear receptors including chicken ovalbumin upstream promoter transcription factor (COUP-TF) and estrogen-related receptor alpha (ERRalpha). We demonstrated that the peroxisome proliferator-activated receptor alpha/9-cis-retinoic acid receptor alpha (PPARalpha/RXRalpha) heterodimer complex can also bind to the two hexamer repeat sequences (between site 1 and site 3) arranged as an everted imperfect repeat separated by 14 bp (ER14). Mutations of the putative core elements have shown that these three sites are differentially involved in ERRalpha and PPARalpha/RXRalpha binding. Homodimer of ERRalpha was shown to interact between site 1 and site 3 (ER14). To date, no nuclear receptor is known to bind to response elements over such long intervals. Interestingly, site 1 was shown to be essential for ERRalpha binding while site 3 supports its binding only in the presence of site 1. Furthermore, it was shown that the binding profile of ERRalpha and PPARalpha/RXRalpha are competitive rather than making a high order complex within NRRE-1. At the cellular level, transcriptional activation driven by the PPARalpha/RXRalpha complex was counteracted by the expression of ERRalpha in HeLa cells. These results suggest that ERRalpha and PPARalpha/RXRalpha could interfere with each other's function through binding to similar DNA elements, thereby finetuning the transcriptional outcome of the target gene. Our findings suggest a mechanism whereby multiple nuclear receptors can activate or repress DNA binding or transcription via a single pleiotropic regulatory element.

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