Search results for "Microbodies"
showing 10 items of 41 documents
The analysis of modified peroxisome proliferator responsive elements of the peroxisomal bifunctional enzyme in transfected HepG2 cells reveals two re…
1995
AbstractPeroxisome proliferators (PPs) are non-genotoxic carcinogens in rodents. They can induce the expression of numerous genes via the heterodimerization of two members of the steroid hormone receptor superfamily, called the peroxisome proliferator-activated receptor (PPAR) and the 9-cis retinoic acid receptor (RXR). Many of the PP responsive genes possess a peroxisome proliferator response element (PPRE) formed by two TGACCT-related motifs. The bifunctional enzyme (HD) PPRE contains 3 such motifs, creating DR1 and DR2 sequences. PPAR and RXR regulate transcription via the DR1 element while DR2 modulates the expression of the gene via auxiliary factors in HepG2 cells.
Influence of peroxisome proliferators on phosphoprotein levels in human and rat hepatic-derived cell lines.
1995
To elucidate the effect of peroxisome proliferators on the signal-transduction pathway, we have compared the effect of ciprofibrate, an hypolipaemic agent, on the overall phosphoprotein level between rat and human well differentiated hepatic derived cell lines. The phosphorylation status of several phosphoproteins in the rat Fao cell line was increased by the drug while no changes were observed in the human HepG2 cell line. In rat Fao cells, this increase, which is concentration and time dependent, can be as much as eightfold for 20-kDa and 22-kDa proteins. Wy-14,643, a non-fibrate molecule and a more potent peroxisome proliferator than ciprofibrate, increased the phosphorylation status of …
Respiration and low cAMP-dependent protein kinase activity are required for high-level expression of the peroxisomal thiolase gene in Saccharomyces c…
1996
Transcription of genes for peroxisomal proteins is repressed by glucose and induced by oleate. At least for the peroxisomal thiolase gene (POT1) there is a third regulatory mechanism, mediated by the transcription factor Adr1p, which is responsible for the high-level expression of the gene in stationary phase. Here we show that a region in the POT1 promoter that extends from positions -238 to -152 mediates this mechanism, and we suggest that Adr1p acts indirectly on POT1. We have also analyzed the role of the cAMP-dependent protein kinase (PKA) in the transcriptional regulation of POT1. PKA exerts a negative control: the high, unregulated PKA activity in a bcy1 mutant maintains POT1 transcr…
Phylogenetic analysis of the thiolase family. Implications for the evolutionary origin of peroxisomes
1992
The thiolase family is a widespread group of proteins present in prokaryotes and three cellular compartments of eukaryotes. This fact makes this family interesting in order to study the evolutionary process of eukaryotes. Using the sequence of peroxisomal thiolase from Saccharomyces cerevisiae recently obtained by us and the other known thiolase sequences, a phylogenetic analysis has been carried out. It shows that all these proteins derived from a primitive enzyme, present in the common ancestor of eubacteria and eukaryotes, which evolved into different specialized thiolases confined to various cell compartments. The evolutionary tree obtained is compatible with the endosymbiotic theory fo…
ADR1 and SNF1 Mediate Different Mechanisms in Transcriptional Regulation of Yeast POT1 Gene
1994
We studied the consequences of adr1 and snf1 mutations on POT1 gene expression in different growth conditions. The results obtained reveal that ADR1 and SNF1 genes affect POT1 transcription in different ways: ADR1 has a minor role in derepression in low concentration of glucose but is essential for activation in stationary phase whereas SNF1 is essential for derepression and activation, although it does not seem to be directly involved in the molecular mechanism of activation in stationary phase.
Peroxisome proliferators and peroxisome proliferator activated receptors (PPARs) as regulators of lipid metabolism.
1997
Peroxisome proliferation (PP) in mammalian cells, first described 30 years ago, represents a fascinating field of modern research. Major improvements made in its understanding were obtained through basic advances that have opened up new areas in cell biology, biochemistry and genetics. A decade after the first report on PP, a new metabolic pathway (peroxisomal beta-oxidation) and its inducibility by peroxisome proliferators were discovered. More recently, a new type of nuclear receptor, the peroxisome proliferator-activated receptor (PPAR), has been described. The first PPAR was discovered in 1990. Since then, many other PPARs have been characterized. This original class of nuclear receptor…
The POT1 gene for yeast peroxisomal thiolase is subject to three different mechanisms of regulation
1992
The Saccharomyces cerevisiae POT1 gene is, as are other yeast peroxisomal protein genes, inducible by fatty acids and repressible by glucose. We have now found that it is also induced during the stationary phase of the culture. To investigate these three regulatory circuits, we have studied the mRNA levels of regulatory mutants as well as the changes in chromatin structure upon gene activation. We conclude that the regulation of transcriptional activity in glucose repression, oleate induction, and stationary phase induction follow different molecular mechanisms. We suggest that this multiplicity of regulatory mechanisms may represent a general rule for the yeast peroxisomal protein genes.
Proteins and enzymes of the peroxisomal membrane in mammals.
1993
Proteins of the peroxisomal membrane can be schematically divided into two groups, one being made up of more or less characterized proteins with generally unknown functions and the other consisting of enzyme activities of which the corresponding proteins have not been characterized. In the present report, these proteins and enzymes are described with the addition of unpublished results regarding their induction by peroxisome proliferators at the post-transcriptional level. Integral membrane proteins (IMPs) can be isolated using an alkaline solution of sodium carbonate. A dozen of preponderant IMPs can be seen on sodium dodecyl sulfate polyacrylamide gel electrophoresis, and the major band c…
Preparation of a dansylated fibrate, a new fluorescent tool to study peroxisome proliferation. Effect on hepatic-derived cell lines.
1997
The synthesis of a dansylated fibrate (DNS-X) has been performed in order to identify the cellular affinity sites of peroxisome proliferators and to establish the subcellular localization of such molecules. DNS-X has been obtained by coupling the dansy1 chloride with the amine resulting from the bezafibrate alkaline hydrolysis. The purified DNS-X has been further characterized by spectrum analysis (UV-Vis, fluorescence, [1H]/[13C]-NMR and mass). At 250 microM and incubated for 48 h with the rat hepatic derived cells (Fao cells), DNS-X stimulates 12-fold the palmitoyl-CoA oxidase, a peroxisome proliferation marker enzyme. This increase is comparable to the one obtained with well known peroxi…
Medical significance of peroxisome proliferator-activated receptors.
1999
Peroxisome proliferator-activated receptors (PPAR) were discovered in 1990, ending 25 years of uncertainty about the molecular mechanisms of peroxisome proliferation. Subsequently, PPARs have improved our understanding of adipocyte differentiation. But there is more to PPARs than solving a puzzle about an organelle (the peroxisome) long considered an oddity, and their medical significance goes beyond obesity too. Enhanced PPAR type alpha expression protects against cardiovascular disorders though the role of enhanced PPARgamma expression seems less favourable. PPAR mechanisms, mainly via induction of more differentiated cell phenotypes, protect against some cancers. The differentiation of m…