scholarly journals Thyromimetic mode of action of peroxisome proliferators: activation of ‘malic’ enzyme gene transcription

1996 ◽  
Vol 319 (1) ◽  
pp. 241-248 ◽  
Author(s):  
Rachel HERTZ ◽  
Vera NIKODEM ◽  
Alumit BEN-ISHAI ◽  
Inna BERMAN ◽  
Jacob BAR-TANA
Keyword(s):  
Thyroid Hormone ◽  
Transcriptional Activation ◽  
Malic Enzyme ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferators ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enzyme Gene ◽  
Hormone Response Element ◽  
Malic Enzyme Gene ◽  
Glycerol 3 Phosphate Dehydrogenase

Peroxisome proliferators induce thyroid-hormone-dependent liver activities, e.g. ‘malic’ enzyme, mitochondrial glycerol-3-phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, S14 [Hertz, Aurbach, Hashimoto and Bar-Tana (1991) Biochem. J. 274, 745–751]. Here we report that the thyromimetic effect of peroxisome proliferators with respect to ‘malic’ enzyme results from transcriptional activation of the ‘malic’ enzyme gene, mediated by binding of the peroxisome proliferator activated receptor (PPARα)/retinoid X receptor (RXRα) heterodimer to a 5´-flanking enhancer of the ‘malic’ enzyme promoter. The enhancer involved is distinct from the thyroid hormone response element of the ‘malic’ enzyme promoter and is partly homologous with that which mediates transcriptional activation of peroxisomal acyl-CoA oxidase by peroxisome proliferators. Hence transcriptional activation of thyroid-hormone-dependent liver genes by xenobiotic or endogenous amphipathic carboxylates collectively defined as peroxisome proliferators is mediated by a transduction pathway similar to that involved in transcriptional activation of peroxisomal β-oxidative genes and distinct from that which mediates thyroid hormone action.

scholarly journals The peroxisome proliferator activated receptor regulates malic enzyme gene expression.

1994 ◽  
Vol 269 (43) ◽  
pp. 26754-26758
Author(s):  
H Castelein ◽  
T Gulick ◽  
P E Declercq ◽  
G P Mannaerts ◽  
D D Moore ◽  
...  
Keyword(s):  
Gene Expression ◽  
Malic Enzyme ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enzyme Gene ◽  
Malic Enzyme Gene

scholarly journals The Effect of Thyroid Hormone on the Chromatin Structure and Expression of the Malic Enzyme Gene in Hepatocytes

1988 ◽  
Vol 2 (7) ◽  
pp. 619-626 ◽  
Author(s):  
Stephen J. Usala ◽  
W. Scott Young ◽  
Hajimu Morioka ◽  
Vera M. Nikodem
Keyword(s):  
Thyroid Hormone ◽  
Chromatin Structure ◽  
Malic Enzyme ◽  
Enzyme Gene ◽  
Malic Enzyme Gene

scholarly journals Hexachlorobenzene, a Dioxin-Type Compound, Increases Malic Enzyme Gene Transcription through a Mechanism Involving the Thyroid Hormone Response Element1

Endocrinology ◽  
1999 ◽  
Vol 140 (9) ◽  
pp. 4142-4151 ◽  
Author(s):  
Andrea I. Loaiza-Pérez ◽  
Maria-Teresa Seisdedos ◽  
Diana L. Kleiman de Pisarev ◽  
Horacio A. Sancovich ◽  
Andrea S. Randi ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Gene Transcription ◽  
Malic Enzyme ◽  
Hormone Response ◽  
Enzyme Gene ◽  
Type Compound ◽  
Malic Enzyme Gene

scholarly journals Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators.

1995 ◽  
Vol 15 (6) ◽  
pp. 3012-3022 ◽  
Author(s):  
S S Lee ◽  
T Pineau ◽  
J Drago ◽  
E J Lee ◽  
J W Owens ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Target Genes ◽  
Receptor Gene ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferators ◽  
Targeted Disruption ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cycle Regulation ◽  
Insight Into

To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in rodents, we disrupted the ligand-binding domain of the alpha isoform of mouse PPAR (mPPAR alpha) by homologous recombination. Mice homozygous for the mutation lack expression of mPPAR alpha protein and yet are viable and fertile and exhibit no detectable gross phenotypic defects. Remarkably, these animals do not display the peroxisome proliferator pleiotropic response when challenged with the classical peroxisome proliferators, clofibrate and Wy-14,643. Following exposure to these chemicals, hepatomegaly, peroxisome proliferation, and transcriptional-activation of target genes were not observed. These results clearly demonstrate that mPPAR alpha is the major isoform required for mediating the pleiotropic response resulting from the actions of peroxisome proliferators. mPPAR alpha-deficient animals should prove useful to further investigate the role of this receptor in hepatocarcinogenesis, fatty acid metabolism, and cell cycle regulation.

scholarly journals Wnt/β-catenin Pathway-Mediated PPARδ Expression during Embryonic Development Differentiation and Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 1854
Author(s):  
Tabinda Sidrat ◽  
Zia-Ur Rehman ◽  
Myeong-Don Joo ◽  
Kyeong-Lim Lee ◽  
Il-Keun Kong
Keyword(s):  
Embryonic Development ◽  
Transcriptional Activation ◽  
Target Gene ◽  
Developmental Stages ◽  
Embryonic Stem ◽  
Hereditary Diseases ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Stem Cell Regulation ◽  
Early Developmental

The Wnt/β-catenin signaling pathway plays a crucial role in early embryonic development. Wnt/β-catenin signaling is a major regulator of cell proliferation and keeps embryonic stem cells (ESCs) in the pluripotent state. Dysregulation of Wnt signaling in the early developmental stages causes several hereditary diseases that lead to embryonic abnormalities. Several other signaling molecules are directly or indirectly activated in response to Wnt/β-catenin stimulation. The crosstalk of these signaling factors either synergizes or opposes the transcriptional activation of β-catenin/Tcf4-mediated target gene expression. Recently, the crosstalk between the peroxisome proliferator-activated receptor delta (PPARδ), which belongs to the steroid superfamily, and Wnt/β-catenin signaling has been reported to take place during several aspects of embryonic development. However, numerous questions need to be answered regarding the function and regulation of PPARδ in coordination with the Wnt/β-catenin pathway. Here, we have summarized the functional activation of the PPARδ in co-ordination with the Wnt/β-catenin pathway during the regulation of several aspects of embryonic development, stem cell regulation and maintenance, as well as during the progression of several metabolic disorders.

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