Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effects of TNF-alpha on the mRNAs coding for the peroxisome proliferator activated receptor alpha (PPAR-alpha), and for catalase (Cat), acyl-CoA oxidase (AOX), multifunctional enzyme (PH), and beta-actin in rat liver. Total RNA was isolated from livers of male SD-rats 16 h after administration of a single dose of 25 microg TNF-alpha and mRNAs were analyzed by a novel dot blot RNase protection assay. The mRNAs for PPAR-alpha and for Cat, AOX and PH were significantly reduced by TNF-treatment. In addition, the level of PPAR-alpha protein was also decreased after TNF. In contrast, the mRNA for beta-actin was markedly increased implying that the effect of TNF on PPAR-alpha and the peroxisomal mRNAs is highly selective. This effect may have important implications in perturbation of the lipid metabolism induced by TNF-alpha.
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PMID:TNF-alpha downregulates the peroxisome proliferator activated receptor-alpha and the mRNAs encoding peroxisomal proteins in rat liver. 925 57

The peroxisome proliferator activated receptor alpha (PPAR) is a member of the steroid/hormone receptor superfamily that mediates the peroxisome proliferator-dependent transcriptional activation of genes encoding several peroxisomal and microsomal enzymes as well as peroxisome proliferation. Human liver is refractory to the pathological effects of peroxisome proliferators that are seen in mice. With the use of RNase protection assays, the ratio of hepatic PPAR alpha mRNA to beta-actin mRNA was found to be 1 order of magnitude lower in humans than that observed in mice. In addition, the isolation of human cDNA for PPAR alpha that does not encode a functional PPAR because it lacks exon 6 as a result of alternate RNA splicing suggested that this process might also diminish the expression of PPAR alpha. RNase protection analysis of total RNA revealed the presence of splice variants lacking exon 6 at significant levels in all 10 human liver samples examined. Supershift analysis using the CYP4A6-Z peroxisome proliferator response element and antisera specific for PPAR alpha revealed easily detectable amounts of PPAR alpha DNA binding activity in mouse liver lysates, whereas human liver lysates contained > 10-fold lower amounts of PPAR alpha DNA binding activity. In contrast to mouse lysates, the amount of PPAR alpha binding in human lysates was generally less than that of other unidentified proteins. These results suggest that although humans retain the coding potential for a functional receptor, the low levels of PPAR alpha expression in liver may be insufficient to compete effectively with other proteins that bind to peroxisome proliferator response elements.
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PMID:Peroxisome proliferator activated receptor-alpha expression in human liver. 944 28

It has been difficult to induce the expected sebocyte differentiation in vitro with dihydrotestosterone (DHT). We reasoned that our culture system lacks differentiating factors, and peroxisome proliferator-activated receptors (PPARs) were the prime candidates. We tested PPAR activators informative about diverse PPAR subtypes, with and without DHT (10(-6) M): BRL-49653 (10(-6) M, PPAR-gamma), WY-14643 (10(-6) M, PPAR-alpha), and linoleic acid (LIN, 10(-4) M, PPAR-delta). Treatments were added in serum-free medium to cultures of rat preputial sebocytes. Control, DHT, BRL and BRL + DHT treatments caused 11, 25, 66 and 80%, respectively, of preputial cell colonies to differentiate into lipid-forming colonies (LFCs) (p < 0.001). WY induced 20% and LIN over 95% LFC formation. PPAR-gamma mRNA was identified in preputial sebocytes by the RNase protection assay. These data suggest that differentiation of sebocytes is transduced by PPARs and have implications for the development of new treatments for acne.
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PMID:Mechanisms of androgen induction of sebocyte differentiation. 955 23

Peroxisomes and the activities of their enzymes have been reported to be significantly reduced in various types of tumors including the colon carcinoma. Therefore, the present study was designed to investigate the gene expression of several peroxisomal proteins in human colon carcinoma and additionally those of the peroxisome proliferator activated receptor alpha (PPARalpha) and PEX5, a receptor protein involved in the import of most peroxisomal matrix proteins. Samples from adenocarcinomas and adjacent normal colon were analyzed by immunohistochemistry and western blotting. The mRNA content was assessed by a novel sensitive dot blot RNase protection assay and northern blotting. By immunohistochemistry, peroxisomes were distinctly visualized in normal colonocytes but were not detected in colon carcinoma cells. The protein levels of catalase (CAT), acyl-CoA oxidase as well as the 22 and 70 kDa peroxisomal membrane proteins (PMP22 and PMP70) were all significantly decreased in carcinomas. The corresponding mRNAs for CAT and PMP70, however, were unchanged. In contrast, the mRNA of PEX5 was significantly increased. The expression of PPARalpha was not altered in tumors, neither at protein nor mRNA levels. These observations show that the reduction of peroxisomes and their proteins in colon carcinoma is not due to a generalized reduction of transcription of their genes. It seems more likely that this phenomenon is regulated at a post-transcriptional or translational level. Alternatively, and more likely, an impairment of the biogenesis of the organelle could account for the paucity of peroxisomes in colon carcinoma.
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PMID:Impairment of peroxisomal biogenesis in human colon carcinoma. 1035 77

An early event in acute and chronic inflammation and associated diseases such as atherosclerosis and rheumatoid arthritis is the induced expression of specific adhesion molecules on the surface of endothelial cells (ECs), which subsequently bind leukocytes. Peroxisome proliferator-activated receptors (PPARs), members of the nuclear receptor superfamily of transcription factors, are activated by fatty acid metabolites, peroxisome proliferators, and thiazolidinediones and are now recognized as important mediators in the inflammatory response. Whether PPAR activators influence the inflammatory responses of ECs is unknown. We show that the PPAR activators 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), Wyeth 14643, ciglitazone, and troglitazone, but not BRL 49653, partially inhibit the induced expression of vascular cell adhesion molecule-1 (VCAM-1), as measured by ELISA, and monocyte binding to human aortic endothelial cells (HAECs) activated by phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide. The "natural" PPAR activator 15d-PGJ(2) had the greatest potency and was the only tested molecule capable of partially inhibiting the induced expression of E-selectin and neutrophil-like HL60 cell binding to PMA-activated HAECs. Intracellular adhesion molecule-1 induction by PMA was unaffected by any of the molecules tested. Both PPAR-alpha and PPAR-gamma mRNAs were detected in HAECs by using reverse transcription-polymerase chain reaction and a ribonuclease protection assay; however, we have yet to determine which, if any, of the PPARs are mediating this process. These results suggest that certain PPAR activators may help limit chronic inflammation mediated by VCAM-1 and monocytes without affecting acute inflammation mediated by E-selectin and neutrophil binding.
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PMID:Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction. 1047 50

Activated peroxisome proliferator activated receptor alpha (PPAR alpha) protects against the cellular inflammatory response, and is central to fatty acid-mediated upregulation of the gene encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS). We have previously demonstrated both PPAR alpha and mHS expression in brain, implying that brain-targeted PPAR alpha activators may likewise up-regulate mHS expression in brain. Thus, to attempt pharmacological activation of brain PPAR alpha in vivo, we have administered to rats two drugs with previously defined actions in rat brain, namely the PPAR alpha-selective activator ciprofibrate and the pan-PPAR activator valproate. Using the sensitive and discriminatory RNase protection co-assay, we demonstrate that both ciprofibrate and valproate induce mHS expression in liver, the archetypal PPAR alpha-expressing organ. Furthermore, ciprofibrate potently increases mHS mRNA abundance in rat brain, together with lesser increases in two other PPAR alpha-regulated mRNAs. Thus we demonstrate, for the first time, up-regulation of expression of PPAR alpha-dependent genes including mHS in brain, with implications in the increased elimination of neuro-inflammatory lipids and concomitant increased production of neuro-protective ketone bodies.
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PMID:The peroxisome proliferator-activated receptor alpha-selective activator ciprofibrate upregulates expression of genes encoding fatty acid oxidation and ketogenesis enzymes in rat brain. 1198 31