Species differences in response to diethylhexylphthalate: suppression of apoptosis, induction of DNA synthesis and peroxisome proliferator activated receptor alpha-mediated gene expression

2000 ◽  
Vol 74 (2) ◽  
pp. 85-91 ◽  
Author(s):  
Susan C. Hasmall ◽  
Neil H. James ◽  
Neil Macdonald ◽  
Anthony R. Soames ◽  
Ruth A. Roberts
Keyword(s):  
Gene Expression ◽  
Dna Synthesis ◽  
Species Differences ◽  
Peroxisome Proliferator ◽  
Apoptosis Induction ◽  
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.

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 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

Species differences in induction of hepatic enzymes by BM 17.0744, an activator of peroxisome proliferator-activated receptor alpha (PPARα)

1999 ◽  
Vol 73 (8-9) ◽  
pp. 440-450 ◽  
Author(s):  
Kirstin Meyer ◽  
Alfred Völkl ◽  
Richard Endele ◽  
Hans-Frieder Kühnle ◽  
Johannes Pill
Keyword(s):  
Species Differences ◽  
Peroxisome Proliferator ◽  
Hepatic Enzymes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha
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