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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial peroxisomes were investigated in normal and diabetic rats. Catalase and acyl-CoA oxidase activities were increased in the diabetic rat heart and immunoblot analysis showed that both enzyme proteins were markedly enhanced in diabetic heart homogenates. After immunoenzyme staining, catalase and acyl-CoA oxidase were localized in fine granules in the myocardium, which were increased in number in diabetic rats. The numerical density of the granules stained for catalase was increased 1.7 times and that for acyl-CoA oxidase 1.8 times, compared with controls. Protein A-gold labeling for catalase and acyl-CoA oxidase was present in myocardial peroxisomes. The labeling density for both enzymes was increased in diabetic rats by 1.6 times for catalase and 1.5 times for acyl-CoA oxidase, compared with controls. The results indicate that myocardial peroxisomes are increased in the diabetic rat and that this proliferation is accompanied by an increase in catalase and acyl-CoA oxidase activities.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Proliferation of myocardial peroxisomes in experimental rat diabetes: a biochemical and immunocytochemical study. 136 21

Degradation of the peroxisomal enzymes fatty acyl-CoA oxidase and catalase was studied in hepatocytes isolated from rats treated with clofibrate and from control rats. Hepatocytes were incubated in the absence of amino acids in order to ensure maximal flux through the autophagic pathway and in the presence of cycloheximide to inhibit protein synthesis. (1) Degradation of the two peroxisomal enzymes in hepatocytes from clofibrate-fed rats, but not in hepatocytes from control rats, was much faster than that of other intracellular enzymes. This increased degradation of the peroxisomal enzymes was almost completely prevented by 3-methyladenine, an inhibitor of macroautophagic sequestration. (2) The increased degradation of the peroxisomal enzymes was also inhibited by a long-chain (C16:0) and a very-long-chain (C26:0) fatty acid, but not by C12:0, a medium-chain fatty acid, or by C8:0, a short-chain fatty acid. These results provide direct evidence for the proposal that autophagic sequestration can be highly selective [(1987) Exp. Mol. Pathol. 46, 114-122]. It is concluded that preferential autophagy of peroxisomes is prevented when these organelles are supplied with their fatty acid substrates.
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PMID:Autophagic degradation of peroxisomes in isolated rat hepatocytes. 161 6

A recently developed transformation system has been used to facilitate the sequential disruption of the Candida tropicalis chromosomal POX4 and POX5 genes, encoding distinct isozymes of the acyl coenzyme A (acyl-CoA) oxidase which catalyzes the first reaction in the beta-oxidation pathway. The URA3-based transformation system was repeatedly regenerated by restoring the uracil requirement to transformed strains, either through selection for spontaneous mutations or by directed deletion within the URA 3 coding sequence, to permit sequential gene disruptions within a single strain of C. tropicalis. These gene disruptions revealed the diploid nature of this alkane- and fatty acid-utilizing yeast by showing that it contains two copies of each gene. A comparison of mutants in which both POX4 or both POX5 genes were disrupted revealed that the two isozymes were differentially regulated and displayed unique substrate profiles and kinetic properties. POX4 was constitutively expressed during growth on glucose and was strongly induced by either dodecane or methyl laurate and to a greater extent than POX5, which was induced primarily by dodecane. The POX4-encoded isozyme demonstrated a broad substrate spectrum in comparison with the narrow-spectrum, long-chain oxidase encoded by POX5. The absence of detectable acyl-CoA oxidase activity in the strain in which all POX4 and POX5 genes had been disrupted confirmed that all functional acyl-CoA oxidase genes had been inactivated. This strain cannot utilize alkanes or fatty acids for growth, indicating that the beta-oxidation pathway has been functionally blocked.
Mol Cell Biol 1991 Sep
PMID:Determination of Candida tropicalis acyl coenzyme A oxidase isozyme function by sequential gene disruption. 187 24

Peroxisomes are particularly abundant in the proximal tubules of the mammalian kidney. We describe the immunocytochemical localization of catalase and three peroxisomal lipid beta-oxidation enzymes: acyl-CoA oxidase, bifunctional protein (enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase) and 3-ketoacyl-CoA thiolase, in human renal biopsies fixed with glutaraldehyde and embedded in Epon. For light microscopy of semithin sections, satisfactory immunostaining required removal of the resin and controlled proteolytic digestion followed by the indirect immunoperoxidase technique. Brief etching of ultrathin sections with alkoxide followed by the protein A-gold method were used for electron microscopic localization of the enzymes. The immunoreactive peroxisomes were distinctly visualized in proximal tubular epithelial cells with no staining of any other cell organelles. The results establish the presence of catalase and of peroxisomal lipid beta-oxidation system proteins in human kidney. The immunocytochemical procedure described herein provides a simple approach for the investigation of peroxisomal structure and function in human renal biopsies processed for ultrastructural studies.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:Immunocytochemical demonstration of peroxisomal enzymes in human kidney biopsies. 289 31

The compartmentalization of catalase, fatty acyl-CoA oxidase and urate oxidase was examined in the livers of mice, rats and guinea pigs, using the technique of digitonin extraction in order to avoid the trauma associated with centrifugation procedures. The results are interpreted as indicating that an appreciable proportion of catalase activity occurs in the cytoplasmic compartment of these cells. Following treatment of the animals with clofibrate, the specific activity in both peroxisomal and cytoplasmic compartments was increased, with a higher proportion of cytoplasmic catalase being evident in mice. The results for catalase were compared with those for fatty acyl-CoA oxidase and urate oxidase both of which were indicated as showing a closer association with the peroxisomal compartment than was the case for catalase. These data have been discussed in relation to their significance on present understanding of peroxisomal structure and function.
Mol Cell Biochem 1988 Oct
PMID:On the compartmentalization of catalase, fatty acyl-CoA oxidase and urate oxidase in mammalian livers, and the influence of clofibrate treatment on this microlocalization. 320 Feb 53

Newly synthesized peroxisomal proteins enter preexisting peroxisomes posttranslationally in vivo, generally without proteolytic processing. An efficient reconstitution of this process in vitro together with cloned DNAs for peroxisomal proteins would make possible investigation of the molecular information that targets proteins to peroxisomes. We have previously reported the isolation of clones for Candida tropicalis peroxisomal proteins; here we describe the association (and possible import) of peroxisomal proteins with peroxisomes in vitro. C. tropicalis was grown in a medium containing Brij 35, resulting in the induction of a moderate number of medium-sized peroxisomes. These peroxisomes, isolated in a sucrose gradient, had a catalase latency of 54% and were sufficiently stable to be concentrated and used in an import assay. The reticulocyte lysate translation products of total RNA from oleate-grown cells were incubated with the peroxisomes at 26 degrees C in the presence of 50 mM KCl, protease inhibitors, 0.5 M sucrose, 2.5 mM MOPS (morpholinepropanesulfonic acid) (pH 7.2), and 0.5 mM EDTA. Ten major translation products (which could be immunoprecipitated with antiserum against peroxisomal protein) became progressively associated with the peroxisomes during the first 30 min of incubation (some up to approximately 70%). These include acyl coenzyme A oxidase and the trifunctional protein hydratase-dehydrogenase-epimerase. This association did not occur at 4 degrees C nor did it occur if the peroxisomes were replaced with mitochondria.
Mol Cell Biol 1987 May
PMID:Efficient association of in vitro translation products with purified stable Candida tropicalis peroxisomes. 360 Jun 48

The development of peroxisomes in the cells of Candida tropicalis grown on oleic acid was accompanied by a markedly high expression of peroxisomal proteins. On the basis of this finding, the nuclear DNA library of this yeast was screened by differential hybridization, and 102 clones of oleic acid-inducible sequences were isolated. Seven coding regions were found to form clusters in three stretches of the genomic DNA. Five of the regions were identified as genes for peroxisomal polypeptides (PXPs). The coding sequence for PXP-2 hybrid selected an additional mRNA for PXP-4, the subunit of long-chain acyl coenzyme A oxidase, which was the most abundant PXP. PXP-2 and PXP-4 were close in apparent molecular weight and generated similar peptides when digested with a protease. The gene for PXP-4 was adjacent to that for PXP-2 on the genome and also hybridized to the mRNA coding for PXP-5. These and other similar results suggest that the genes for the peroxisomal proteins of this organism arose by duplication of a few ancestral genes.
Mol Cell Biol 1984 Oct
PMID:High-level expression and molecular cloning of genes encoding Candida tropicalis peroxisomal proteins. 650 42

We have previously described mutant S. cerevisiae that are defective in peroxisome biogenesis (peb mutants) (Zhang, J. W., Y. Han, and P. B. Lazarow. 1993. J. Cell Biol. 123:1133-1147.). In some mutants, peroxisomes are undetectable. Other mutants contain normal-looking peroxisomes but fail to package subsets of peroxisomal proteins into the organelle (Zhang, J. W., C. Luckey, and P. B. Lazarow. 1993. Mol. Biol. Cell. 4:1351-1359.). In peb1 (pas7) cells, for example, the peroxisomes contain proteins that are targeted by COOH-terminal tripeptides and contain acyl-CoA oxidase (which is probably targeted by internal oligopeptides), but fail to import thiolase (which is targeted by an NH(2)-terminal 16-amino acid sequence). These and other data suggest that there are three branches in the pathway for the import of proteins into peroxisomes, each of which contains a receptor for one type of peroxisomal topogenic information. Here, we report the cloning and characterization of the PEB1 gene, that encodes a 42,320-Da hydrophilic protein with no predicted transmembrane segment. The protein contains six WD repeats, a motif which has been found in 27 proteins involved in diverse cellular functions. The PEB1 gene product was tagged with the hemagglutinin epitope and found to rescue thiolase import in the peb1 null mutant. The epitope-tagged protein was shown to be inside of peroxisomes by immunofluorescence, digitonin permeabilization, equilibrium density centrifugation, immunoelectron microscopy, and proteinase K protection studies. The PEB1 gene product does not cleave the thiolase-targeting sequence. It may function to draw thiolase into peroxisomes.
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PMID:PEB1 (PAS7) in Saccharomyces cerevisiae encodes a hydrophilic, intra-peroxisomal protein that is a member of the WD repeat family and is essential for the import of thiolase into peroxisomes. 753 4

The mouse peroxisome proliferator-activated receptor alpha (mP-PAR alpha) can activate transcription from the CYP4A6 promoter in transient cotransfection experiments in the absence (intrinsic transactivation) or presence of added peroxisome proliferator. However, mPPAR alpha-G, in which glycine is substituted for Glu282, exhibits very low intrinsic transactivation and responds fully to added peroxisome proliferators. The two receptors, when expressed in COS-1 cells, are nuclear in localization, are expressed at similar levels, have similar stability, and bind DNA in vitro with similar efficiency. The phenotypic difference in intrinsic transactivation is not altered by overexpression of the human retinoid X receptor alpha. The mPPAR alpha-G mutant receptor displays a higher EC50 for pirinixic acid and for 5,8,11,14-eicosatetraynoic acid than the wild-type PPAR alpha. This difference in the apparent EC50 value is independent of the cell lines used and indicates that the Glu282 to glycine substitution alters the response of mPPAR alpha to peroxisome proliferators. The EC50 values obtained for each receptor with the CYP4A6 reporter construct are lower than those for a reporter derived from the acyl-CoA oxidase gene. In general, an inverse relation is evident between the apparent EC50 values and the extent of intrinsic transactivation observed. The difference in intrinsic transactivation may reflect the presence of an endogenous activator at a concentration that is not sufficient to activate the mPPAR alpha-G but that is sufficient to effect the intrinsic transactivation seen for the wild-type mPPAR alpha.
Mol Pharmacol 1995 Sep
PMID:A single amino acid change in the mouse peroxisome proliferator-activated receptor alpha alters transcriptional responses to peroxisome proliferators. 756 38

It is now clear that peroxisomes play a crucial role in many cellular processes, including the beta-oxidation of very long chain fatty acids. Recently, mammalian peroxisomes have been shown to contain the antioxidant enzymes, superoxide dismutase and glutathione peroxidase, in addition to catalase. The presence of these enzymes in peroxisomes suggests that peroxisomes undergo oxidative stress in normal and disease states. As an indicator of the potential impact of an oxidative stress on peroxisomal functions, we evaluated the effect of endotoxin exposure on the beta-oxidation enzyme system in rat liver. Peroxisomes were isolated from liver homogenates by differential and density gradient centrifugations. Endotoxin treatment decreased the beta-oxidation of lignoceric acid to 56% of control values (p < 0.01). The specific activity of the rate limiting enzyme in the system, acyl-CoA oxidase, was decreased to 73% of control values (p < 0.05). Immunoblot analysis revealed a 25% decrease in the 21KD subunit of the acyl-CoA oxidase protein. In contrast, the protein levels of the other enzymes in the pathway, trifunctional protein and 3-ketoacyl-CoA thiolase, were increased by 10 and 15%, respectively. These findings suggest that impairment of beta-oxidation of lignoceric acid by endotoxin treatment is due primarily to a reduction in the activity and protein level of the key enzyme, acyl-CoA oxidase. Oxidative stresses such as endotoxin exposure may have deleterious effects on important peroxisomal functions, such as beta-oxidation of very long chain fatty acids.
Mol Cell Biochem 1994 Jun 29
PMID:Impairment of peroxisomal beta-oxidation system by endotoxin treatment. 783 45


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