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Bratislavske Lekarske Listy Dec 1994Many species of monocellular eukaryots as well as the majority of animal cell and plant tissues show the presence of peroxisomes or microperoxisomes. Their size, shape... (Review)
Review
Many species of monocellular eukaryots as well as the majority of animal cell and plant tissues show the presence of peroxisomes or microperoxisomes. Their size, shape and internal organization may differ in various cellular types significantly. Typical components of animal cell peroxisomes are the membrane, matrix, low density compartment enriched in lipids, and the compartment containing D-amino acid oxidase. The group of four enzymes (catalase, D-amino acid oxidase, L-alpha-OH-acid oxidase) the location of which had been originally discovered in peroxisomes of hepatocytes of rodents was later widened by approximately forty further enzymes. It is though probable that evolution brought along a reduction and loss of various metabolic functions of peroxisomes and a decrease in the number of enzymes. Peroxisomes are characterized by high variability of the enzymatic content in dependence on the nutritional conditions and the effect of xenobiotics. Fasting, diabetes mellitus, high-lipid diet, peroxisome proliferators induce several peroxisomal enzymes, especially fatty acids beta-oxidation. The mechanism of the impact of heterogeneous substances on the gene transcription has been clarified recently. Substances as fibrates, retinoic acid, polyunsaturated fatty acids activate specific types of receptors-PPAR (peroxisome proliferators activated receptors) belonging to the superfamily of receptors activated by steroid hormones, thyroid hormones, and D-vitamins. A simultaneous induction of several peroxisomal enzymes can be achieved by the linkage between PPAR and specific areas of promotors of particular genes. Such areas-PPREs (peroxisomal proliferator response elements) with five repeated TGA(A/C/T)CT hexanucleotide sequences separated by one nucleotide were discovered in several peroxisomal genes. It is assumed that the stimulation of transcription can be achieved by the linkage between homodimers, and heterodimers of nuclear receptors on these DNA sections. The majority of peroxisomal proteins is synthesised in the cytoplasm, namely on polysomes being in matured forms. Unimpaired biogenesis of peroxisomes requires membrane transport proteins and presence of signal in polypeptide chain of imported proteins (PTS-peroxisomal targeting signal). The function of PTS in many peroxisomal proteins is fulfilled by the C-terminal tripeptide which is composed of amino acids, namely serine, lysine, and leucine (SKL-tripeptide), respectively by a tripeptide with a very similar composition in amino acids. Aside from this signal, still another signal exists, which is located at the N-end of peroxisomal proteins. The role of membrane proteins 70, 35, 256, 22, 15 kDa, is being discussed in relationship to the functions and diseases caused by impaired biogenesis of peroxisomes. (Fig. 4, Ref. 128.)
Topics: Animals; Humans; Microbodies
PubMed: 7735895
DOI: No ID Found -
The American Journal of Pathology Mar 1973Male wild-type mice (Cs(a) strain) were treated with ethyl-alpha-p-chlorophenoxyisobutyrate (CPIB), a hypolipidemic drug which enhances hepatic catalase synthesis and...
Male wild-type mice (Cs(a) strain) were treated with ethyl-alpha-p-chlorophenoxyisobutyrate (CPIB), a hypolipidemic drug which enhances hepatic catalase synthesis and induces rapid and significant increase in the number of microbody (peroxisome) profiles in liver cells. Numerous microbody profiles, several of them appearing in clusters and retaining membranous continuities, were observed in liver cells of CPIB-treated mice. They showed a significant variation in size and configuration, and the presence or absence of the nucleoid or core did not appear to bear any relation to the size or shape of microbody profiles. Nucleoids were encountered frequently in microbody profiles measuring as small as 0.1 mu in diameter. Numerous continuities between two or more anucleoid and/or nucleoid-containing microbody profiles of different sizes and shapes were seen. These findings are inconsistent with the concept that the smaller peroxisomes are the possible precursors or progenitors of their larger counterparts. Detailed examination of numerous electron micrographs revealed irregular dilatations and tortuosities of the endoplasmic reticulum (ER) containing electron-opaque peroxisomal material displaying the characteristic appearance of matrix and usually containing irregular cores. Transitions of rough ER to smooth ER in which microbody proteins accumulated were also apparent. Numerous continuities between several microbody profiles and continuities between microbody profiles and ER are interpreted as accumulations of peroxisomal proteins in dilated tortuous channels of ER. These observations strongly suggest that the microbody proteins constitute a common pool, circulating constantly in the dilated ER channels. The size, shape and number of microbody profiles appear to reflect the amount of peroxisomal proteins present in the pool. These observations clearly suggest that the microbodies do not exist as individual entities.
Topics: Animal Feed; Animals; Clofibrate; Endoplasmic Reticulum; Liver; Male; Mice; Microbodies; Microscopy, Electron; Organoids; Proteins; Staining and Labeling
PubMed: 4120301
DOI: No ID Found -
Hormone Research 1992A group of receptors termed peroxisome proliferator activated receptors (PPAR), belonging to the nuclear hormone receptor supergene family, might be crucial in... (Review)
Review
Regulation of gene expression by fatty acids and fibric acid derivatives: an integrative role for peroxisome proliferator activated receptors. The Belgian Endocrine Society Lecture 1992.
A group of receptors termed peroxisome proliferator activated receptors (PPAR), belonging to the nuclear hormone receptor supergene family, might be crucial in explaining how a diverse group of apparently unrelated chemicals induce peroxisomal proliferation and a change in the expression of several genes. The activation of these PPAR by peroxisome proliferators, as well as by fatty acids, might reconcile the apparent discrepancy between the two prevailing theories that explain peroxisome proliferation, i.e. the receptor and the fatty acid theory. Although the exact physiological role of PPAR is not yet known, these receptors might have a far more general function than strictly regulating peroxisomal gene expression by changing the expression of numerous genes in response to developmental and nutritional challenges. Much work, however, remains to be performed before a complete picture will emerge.
Topics: Animals; Fatty Acids; Gene Expression Regulation; Humans; Lipid Metabolism; Microbodies; Microsomes; Models, Biological; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Transcription Factors
PubMed: 1339170
DOI: 10.1159/000182557 -
Food and Chemical Toxicology : An... Nov 1993Peroxisomes are subcellular organelles found in all eukaryotic cells. In the liver they are usually round and measure about 0.5-1.0 microns; in rodents they contain a... (Review)
Review
Peroxisomes are subcellular organelles found in all eukaryotic cells. In the liver they are usually round and measure about 0.5-1.0 microns; in rodents they contain a prominent crystalloid core, but this may be absent in newly formed rodent peroxisomes as well as in human peroxisomes. A major role of the peroxisomes is the breakdown of long-chain fatty acids, thereby complementing mitochondrial fatty-acid metabolism. Many chemicals are known to increase the number of peroxisomes in rat and mouse hepatocytes. This peroxisome proliferation is accompanied by replicative DNA synthesis and liver growth. No clear structure-activity relationships are apparent. Many of these peroxisome proliferators contain acid functions that can modulate fatty acid metabolism. Two mechanisms have been proposed for the induction of peroxisome proliferation. One is based on the existence of one or several specific cytosolic receptors that bind the peroxisome proliferator, facilitating its translocation to the cell nucleus and the activation of the expression of specific genes. The second, perhaps more general, hypothesis involves chemically mediated perturbation of lipid metabolism. These two hypotheses are not mutually exclusive. Many peroxisome proliferators have been shown to induce hepatocellular tumours, despite being uniformly non-genotoxic, when administered at high dose levels to rats and mice for long periods. Three mechanisms have been proposed to explain the induction of tumours. One is based on increased production of active oxygen species due to imbalanced production of peroxisomal enzymes; it has been proposed that these reactive oxygen species cause indirect DNA damage with subsequent tumour formation. In rodents, an alternative mechanism is the promotion of endogenous lesions by sustained DNA synthesis and hyperplasia. Thirdly, it is conceivable that sustained growth stimulation may be sufficient for tumour formation. Marked species differences are apparent in response to peroxisome proliferations. Rats and mice are extremely sensitive, and hamsters show an intermediate response while guinea pigs, monkeys and humans appear to be relatively insensitive or non-responsive at dose levels that produce a marked response in rodents. These species differences may be reproduced in vitro using primary culture hepatocytes isolated from a variety of species including humans. The available experimental evidence suggests a strong association and a probable casual link between peroxisome-proliferator-elicited liver growth and the subsequent development of liver tumours in rats and mice. Since humans are insensitive or unresponsive, at therapeutic dose levels, to peroxisome-proliferator-induced hepatic effects, it is reasonable to conclude that the encountered levels of exposure to these non-genotoxic agents do not present a hepatocarcinogenic hazard to humans.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Carcinogens; Cell Division; Female; Humans; Hyperplasia; Hypertrophy; Lipid Metabolism; Liver; Liver Neoplasms; Male; Microbodies; Rodentia; Species Specificity; Structure-Activity Relationship
PubMed: 8258416
DOI: 10.1016/0278-6915(93)90225-n -
Journal of Inherited Metabolic Disease 1995The morphological and morphometric characteristics of peroxisomes in normal human liver and the peroxisomal alterations in the liver of patients with acquired or... (Review)
Review
The morphological and morphometric characteristics of peroxisomes in normal human liver and the peroxisomal alterations in the liver of patients with acquired or congenital non-peroxisomal diseases are reviewed. Secondary peroxisomal changes are observed in steatosis, hepatitis and cirrhosis induced by various agents (viruses, alcohol, drugs, etc.), in cholestasis, in hepatomas, in extra-hepatic cancer with or without liver metastasis, in extrahepatic inflammatory processes, in metabolic disorders affecting metabolism of carbohydrates, lipids and lipoproteins, glycoproteins, amino acids, bilirubin or copper, and in altered thyroid hormone levels. They are recognized as a proliferation of peroxisomes (increased in number and to a lesser extent in surface density and volume density) often accompanied by a minor reduction in size (at most to 68% of the mean diameter in control livers) but very rarely by an increase in mean peroxisomal diameter, and as proliferation-related changes in shape (tails, gastruloid cisternae, funnel-like constrictions, elongation, protrusions) in at least a few of the peroxisomes. These secondary alterations of the peroxisomes are clearly distinguishable from the primary changes in peroxisomes observed in the liver of patients with congenital peroxisomal disorders.
Topics: Humans; Liver; Microbodies; Peroxisomal Disorders
PubMed: 9053551
DOI: 10.1007/BF00711439 -
Biochimie 1997Peroxisome proliferation (PP) in mammalian cells, first described 30 years ago, represents a fascinating field of modern research. Major improvements made in its... (Review)
Review
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 receptors belongs to the superfamily of steroid receptors. With activation of cell signal transduction pathways, the occurrence of PPARs provides, for the first time, a coherent explanation of mechanisms by which PP is triggered. Nevertheless, although many compounds or metabolites are capable of activating PPARs, the natural direct ligands of these receptors have not been, up to now, clearly identified, with, however, the exception of 15-deoxy-12,14-prostaglandin J2 which is the ligand of PPAR gamma 2 while leukotrien LTB4 binds PPAR alpha. At this stage, the hypothesis of some orphan PPARs (ie receptors without known ligand) can not be ruled out. Despite these relatively restrictive aspects, the mechanisms by which activation of PPARs leads to PP become clear; also, coherent hypotheses among which a scenario involving receptor phosphorylation or a heat shock protein (ie HSP 72) can be proposed to explain how PPARs would be activated. The aim of this note is to review recent developments on PPARs, to present members up to now recognized to belong to the PPAR family, their characterization, functions, regulation and mechanisms of activation as well as their involvement in lipid metabolism regulation such as control of beta-oxidation, ketogenesis, fatty acid synthesis and lipoprotein metabolism. As an introducing section, a brief review of the major events between the first report of PP in mammals and the discovery of the first PPAR is given. Another section is devoted to current hypotheses on mechanisms responsible for PPAR activation and PP induction. Rather than an exhaustive presentation of cellular alterations accompanying PP induction, a dynamic overview of the lipid metabolism is provided. By assessing the biological significance of this organellar proliferative process, the reader will be led to conclude that the discovery of PPARs and related gene activation through peroxisome proliferator responsive element (PPRE) makes PP induction one of the most illustrative examples of control that occurs in lipid metabolism.
Topics: Acyl-CoA Oxidase; Animals; Fatty Acids; Gene Expression Regulation, Enzymologic; Humans; Hypolipidemic Agents; Ligands; Lipid Metabolism; Liver; Microbodies; Microsomes; Mitochondria; Oxidation-Reduction; Oxidoreductases; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Transcription Factors; Transcriptional Activation
PubMed: 9209701
DOI: 10.1016/s0300-9084(97)81496-4 -
FEMS Microbiology Letters Dec 1991We studied the influence of specific growth conditions on the induction of beta-oxidation enzymes and rate of microbody proliferation in S. cerevisiae by oleic acid. Of...
We studied the influence of specific growth conditions on the induction of beta-oxidation enzymes and rate of microbody proliferation in S. cerevisiae by oleic acid. Of all conditions tested, highest enzyme levels and microbody numbers were achieved in glucose-limited continuous cultures, supplemented with oleic acids second carbon source. Comparable enzyme levels were observed in identical cultures of peroxisome-deficient (pas) mutants of S. cerevisiae. These experiments showed chemostat cultures on glucose/oleic acid mixtures to be a method of choice for future studies on microbody biogenesis/assembly in constructed, conditional pas mutants.
Topics: Cell Division; Genes, Fungal; Glucose; Microbodies; Mutation; Oleic Acid; Oleic Acids; Promoter Regions, Genetic; Saccharomyces cerevisiae; Transformation, Genetic
PubMed: 1783286
DOI: 10.1016/0378-1097(91)90649-u -
Biochimie 1993In order to investigate the mechanisms of peroxisome biogenesis and to identify components of the peroxisomal import machinery we studied these processes in the yeast... (Review)
Review
In order to investigate the mechanisms of peroxisome biogenesis and to identify components of the peroxisomal import machinery we studied these processes in the yeast Saccharomyces cerevisiae. The forward genetic approach has led to pas-mutants (peroxisomal assembly) which fall into 12 complementation groups and allowed to identify 10 of the corresponding wild-type PAS genes (PAS 1-7, 9, 11 and 12). Recent sequence analysis data of some of these genes are beginning to provide first hints as to the possible function of their gene products. The PAS genes and their corresponding mutants are presently used to address some important questions of peroxisomal biogenesis. Reversed genetics has been started as a complementary approach to characterize especially the function of peroxisomal membrane proteins. For this purpose we describe a technique to isolate highly purified peroxisomes. This led to the identification of 21 polypeptides as constituents of this organelle. Some of them are presently sequenced.
Topics: Adenosine Triphosphatases; Amino Acid Sequence; Biological Evolution; Fungal Proteins; Microbodies; Molecular Sequence Data; Multigene Family; Saccharomyces cerevisiae
PubMed: 8507683
DOI: 10.1016/0300-9084(93)90079-8 -
Current Opinion in Microbiology Dec 2018Glycosomes evolved as specialized system for glycolysis in trypanosomatids. These organelle rely on protein import to maintain function. A machinery of peroxin (PEX)... (Review)
Review
Glycosomes evolved as specialized system for glycolysis in trypanosomatids. These organelle rely on protein import to maintain function. A machinery of peroxin (PEX) proteins is responsible for recognition and transport of glycosomal proteins to the organelle. Disruption of PEX-based import system was expected to be a strategy against trypanosomatids. Recently, a proof of this hypothesis has been presented. Here, we review current information about trypanosomatids' glycosomal transport components as targets for new trypanocidal therapies.
Topics: Animals; Antiprotozoal Agents; Drug Development; Humans; Microbodies; Protein Transport; Protozoan Proteins; Trypanosoma; Trypanosomiasis
PubMed: 30481613
DOI: 10.1016/j.mib.2018.11.003 -
Molecular and Biochemical Parasitology Apr 2019In Trypanosoma cruzi, the causal agent of Chagas disease, the first seven steps of glycolysis are compartmentalized in glycosomes, which are authentic but specialized...
In Trypanosoma cruzi, the causal agent of Chagas disease, the first seven steps of glycolysis are compartmentalized in glycosomes, which are authentic but specialized peroxisomes. Besides glycolysis, activity of enzymes of other metabolic processes have been reported to be present in glycosomes, such as β-oxidation of fatty acids, purine salvage, pentose-phosphate pathway, gluconeogenesis and biosynthesis of ether-lipids, isoprenoids, sterols and pyrimidines. In this study, we have purified glycosomes from T. cruzi epimastigotes, collected the soluble and membrane fractions of these organelles, and separated peripheral and integral membrane proteins by NaCO treatment and osmotic shock. Proteomic analysis was performed on each of these fractions, allowing us to confirm the presence of enzymes involved in various metabolic pathways as well as identify new components of this parasite's glycosomes.
Topics: Chagas Disease; Life Cycle Stages; Microbodies; Proteomics; Protozoan Proteins; Trypanosoma cruzi
PubMed: 30831156
DOI: 10.1016/j.molbiopara.2019.02.008