Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined whether alterations in the growth hormone/insulin-like growth factor-1 axis play a role in the pathogenesis of psoriasis. Serum, urine, full skin biopsies, and suction blister roofs were obtained from patients with psoriasis and from healthy controls. Serum concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 were measured by radioimmunoassay. Growth hormone-binding protein was measured by ligand-mediated immunofunctional assay. Growth hormone concentration in urine was measured by an immunometric assay, and growth hormone receptor-gene expression was measured by RNase protection assay or by quantitative reverse transcriptase polymerase chain reaction in total RNA isolated from epidermal suction blister roofs. Serum concentrations of insulin-like growth factor-1 (249 +/- 12 micrograms per liter, mean +/- SEM, n = 42, and 277 +/- 21 micrograms per liter, n = 9, for psoriatic patients and controls, respectively), insulin-like growth factor binding protein-3 (3.1 +/- 0.08 mg per liter, n = 42, and 3.3 +/- 0.22 mg per liter, n = 9), growth hormone-binding protein (344 +/- 65 pmol per liter, n = 10, and 311 +/- 83 pmol per liter, n = 9), urinary growth hormone excretion during 24 h (12.8 +/- 2.7 microIU per 24 h, n = 12, and 12.3 +/- 1.6 microIU per 24 h, n = 9), and epidermal growth hormone receptor gene expression [32 +/- 12 x 10(3) mRNA transcripts per microgram total RNA (involved skin), n = 11, and 47 +/- 14 x 10(3) mRNA transcripts per microgram total RNA, n = 9] were similar in patients and controls. For insulin-like growth factor-1 and insulin-like growth factor binding protein-3 the values in psoriatic patients were also similar to those in larger control groups, n = 195 and n = 400, respectively. In addition, we found no evidence of local expression of growth hormone or prolactin in full skin punch biopsies from psoriatic involved skin by reverse transcriptase polymerase chain reaction. In conclusion, our results suggest that alterations in the growth hormone/ insulin-like growth factor-1 axis do not play a major role in the pathogenesis of psoriasis.
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PMID:No evidence for involvement of the growth hormone/insulin-like growth factor-1 axis in psoriasis. 934 96

hGrb10alpha (previously named Grb-IR) is a Src-homology 2 domain-containing protein that binds with high affinity to the tyrosine-phosphorylated insulin receptor and insulin-like growth factor-1 receptor. At least two isoforms of human Grb10, (hGrb10alpha and hGrb10beta), which differ in the pleckstrin homology (PH) domain and the N-terminal sequence, have previously been identified in insulin target tissues such as human skeletal muscle and fat cells. Here we report the cloning of the third isoform of the hGrb10 family (hGrb10gamma) from human skeletal muscle and its localization to human chromosome 7. We have also determined the human chromosome localization of Grb7 to 17q21-q22 and Grb14 to chromosome 2. hGrb10gamma contains an intact PH domain and an N-terminal sequence that is present in hGrb10alpha but absent in hGrb10beta. RNase protection assays and Western blot analysis showed that hGrb10alpha and hGrb10gamma are differentially expressed in insulin target cells including skeletal muscle, liver, and adipocyte cells. hGrb10gamma is also expressed in HeLa cells and various breast cancer cell lines. The protein bound with high affinity to the insulin receptor in cells, and the interaction was dependent on the tyrosine phosphorylation of the receptor. hGrb10gamma also underwent insulin-stimulated membrane translocation and serine phosphorylation. hGrb10gamma phosphorylation was inhibited by PD98059, a specific inhibitor of mitogen-activated protein kinase kinase, and wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase. Taken together, our data suggest that hGrb10 isoforms are potential downstream signaling components of the insulin receptor tyrosine kinase and that the PH domain may play an important role in the involvement of these isoforms in signal transduction pathways initiated by insulin and other growth factors.
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PMID:Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma. 936 Sep 86

The response of insulin-like growth factor (IGF) I in acute renal failure was evaluated in a model of radiocontrast nephropathy associated with selective necrosis of medullary thick ascending limbs. In brief, rats were administered radiocontrast medium or vehicle injections for controls after combined inhibition of prostanoids and nitric oxide. Twenty-four hours after the insult, tissue mRNAs for IGF-I, the IGF-I receptor, and IGF-binding proteins (IGFBP) 1 and 3 were assayed in cortex, medulla, and liver by solution hybridization-RNase protection assay, and IGFBPs were measured in serum and tissue by Western ligand blotting. Cortical IGF-1 increased, whereas medullary IGF-I mRNA decreased. Renal IGFBPs decreased, whereas IGFBP-1 mRNA increased. The IGF system in the liver was unchanged. We conclude that general changes in renal IGFBPs in this experimental model of acute renal failure might increase the level of cortical IGF-I in a way that could modulate medullary recovery.
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PMID:The endogenous insulin-like growth factor system in radiocontrast nephropathy. 953 Feb 65

Twenty-four crossbred primiparous sows were used to investigate the influence of insulin administration after weaning on the intrafollicular insulin-like growth factor i (IGF-I) system. Sows received 0.4 i.u. insulin kg-1 bodyweight or an equivalent volume of saline for 3 days (n = 5 insulin; n = 4 saline) or 5 days (n = 5 insulin; n = 6 saline) after weaning or served as untreated controls on day 1 (n = 4). The number and diameters of ovarian follicles were recorded, and fluid was aspirated from the 20 largest follicles for determination of oestradiol and IGF-I by radioimmunoassay and of insulin-like growth factor-binding proteins (IGFBPs) by western ligand blotting. The walls of the follicles were collected for mRNA analysis by RNase protection assay or granulosa cells were collected for estimation of apoptosis by flow cytometry. Insulin treatment resulted in smaller diameters of all follicles (P < 0.05) and tended (P < 0.07) to increase the number of follicles available on day 5 compared with saline-treated animals (19.8 versus 17.8). The concentration of oestradiol in follicular fluid from large (7-10 mm) follicles on days 3 and 5 was reduced (treatment by size class interaction; P < 0.05) by insulin treatment. Insulin also reduced intrafollicular concentrations of IGF-I at days 3 and 5 after weaning (treatment by day interaction; P < 0.02) while the amounts of IGFBP-3 and IGFBPs of molecular mass 30 and 22 kDa decreased from day 3 to day 5 in saline-treated animals only (treatment by day interaction; P < 0.05). Gene expression for IGF-I increased in saline-treated animals but decreased fourfold in insulin-treated sows from day 3 to day 5 (treatment by day interaction; P < 0.002). Gene expression for IGFBP-d decreased (P < 0.04) from day 3 to day 5, while expression of IGFBP-2 was unaffected by treatment or day. Overall, insulin influenced the IGF-I system in a manner consistent with slowing follicular growth and possibly allowed more follicles to become available for ovulation.
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PMID:Influence of insulin on follicular development and the intrafollicular insulin-like growth factor I (IGF-I) system in sows after weaning. 953 43

The objective of this study was to determine the mechanisms by which cortisol down-regulates hepatic insulin-like growth factor-II (IGF-II) gene expression in late gestation. Leader exons 6 and 7 of the ovine IGF-II gene, with their 5'-flanking regions, were first isolated. Characterization of transcription start sites revealed a unique site for exon 6 and three dispersed sites for exon 7. Nuclear run-on assays showed a 5-fold higher transcription rate of the IGF-II gene in liver of adrenalectomized fetuses compared with control animals, suggesting that regulation of IGF-II gene expression by cortisol is at the transcriptional level. RNase protection assays demonstrated hepatic leader exon 7 expression in adrenalectomized fetuses to be more than 2-fold higher than in controls, whereas it was reduced by 50% in cortisol-infused fetuses compared with controls. There was no effect on the expression of other leader exons. Functions of the upstream regulatory region of leader exon 7 (i.e. promoter P4) were investigated by luciferase transient expression. A region of -172 bases downstream relative to the first transcription site of leader exon 7 was shown to retain basal promoter activity and respond to cortisol. These results suggest that cortisol may induce the prenatal decline in ovine hepatic IGF-II expression by suppressing promoter P4 of the IGF-II gene.
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PMID:Transcriptional regulation of insulin-like growth factor-II gene expression by cortisol in fetal sheep during late gestation. 955 19

A variety of adult, non-neural tissues respond to injury by increasing expression of the gene which encodes for insulin-like growth factor-1 (IGF-1). This response is thought to be a key component in the regenerative capacity of these tissues. In contrast, the central nervous system (CNS) has relatively little regenerative capacity following injury. Interestingly, compared to many non-neuronal tissues, little IGF-1 mRNA can be detected in the adult CNS, raising the possibility that its lack of regenerative capacity is related its relative lack of IGF-1 expression. However, in the 2-week-old adolescent CNS IGF-1 mRNA can be detected in numerous brain regions. Therefore, the purpose of this study was to determine the responsiveness of the IGF-1 gene to injury in adolescent CNS tissue, a period in which expression of this gene is relatively abundant. Expression of IGF-1 mRNA was measured by means of a sensitive solution hybridization/RNase protection assay in the parieto-occipital lobes of 2-week-old and adult mice following penetrating injury. Levels of IGF-1 transcript in the injured brains were significantly increased above those of controls in both 2-week-old and adult brains 3-day post injury and remained elevated for 1 week after injury. These observations demonstrate that the adult CNS, like other tissues, can respond to injury by increasing expression of IGF-1 mRNA.
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PMID:Induction of IGF-1 mRNA expression following traumatic injury to the postnatal brain. 963 May 38

The expression of insulin-like growth factor-1 (IGF-1) was examined in subcutaneous (SQ) adipose tissue from 105-day pig fetuses by ribonuclease protection assays and in situ hybridization using a porcine IGF-1 riboprobe. Fetuses were hypophysectomized (hypox) at 70 days of gestation and at 90 days thyroxine (T4) pellets were implanted into some of the hypox fetuses. Fetuses were removed and SQ tissues collected on day 105 of gestation. RNase protection assays followed by scanning laser densitometry revealed that IGF-1 mRNA in SQ adipose tissue in hypox fetuses was significantly decreased to 19.8 +/- 1.2% of control values. T4 treatment increased the expression of IGF-1 by 174 +/- 26.6% of values for hypox fetuses. Using in situ hybridization we showed that fetal hypophysectomy reduced and T4 treatment increased expression of IGF-1 mRNA in the outer SQ adipose tissue layer (P < 0.05). However, T4 treatment after hypox did not influence IGF-1 expression in the inner SQ layer (P > 0.05). IGF-1 was expressed around capillaries, in small fat cells, and in fibroblasts in loose and dense connective tissue. Large fat cells, however, did not express IGF-1. Collectively, we concluded that (1) IGF-1 mRNA was decreased after hypox and increased by T4 treatment in SQ tissue of 105-day fetuses; (2) The expression of the IGF-1 gene was more sensitive to T4 treatment after hypox in outer SQ tissue than in inner SQ tissue; (3) Most stromal cells produced IGF-1 mRNA, and as a result they may influence adipogenesis in the outer layer of SQ adipose tissue; and (4) Once fat cells enlarged, expression of IGF-1 was not detected. Therefore, these studies provide evidence that IGF-1 may mediate the influence of T4 on fetal adipogenesis.
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PMID:The expression of insulin-like growth factor-1 during adipogenesis in vivo: effect of thyroxine. 974 1

Fatty acid transport protein (FATP) was identified by expression cloning strategies (Schaffer, J. E., and Lodish, H. F. (1994) Cell 79, 427-436) and shown by transfection analysis to catalyze the transfer of long-chain fatty acids across the plasma membrane of cells. It is expressed highly in tissues exhibiting rapid fatty acid metabolism such as skeletal muscle, heart, and adipose. FATP mRNA levels are down-regulated by insulin in cultured 3T3-L1 adipocytes and up-regulated by nutrient depletion in murine adipose tissue (Man, M. Z., Hui, T. Y., Schaffer, J. E., Lodish, H. F., and Bernlohr, D. A. (1996) Mol. Endocrinol. 10, 1021-1028). To determine the molecular mechanism of insulin regulation of FATP transcription, we have isolated the murine FATP gene and its 5'-flanking sequences. The FATP gene spans approximately 16 kilobases and contains 13 exons, of which exon 2 is alternatively spliced. S1 nuclease and RNase protection assays revealed the presence of multiple transcription start sites; the DNA sequence upstream of the predominant transcription start sites lacks a typical TATA box. By transient transfection assays in 3T3-L1 adipocytes, the inhibitory action of insulin on FATP transcription was localized to a cis-acting element with the sequence 5'-TGTTTTC-3' from -1347 to -1353. This sequence is very similar to the insulin response sequence found in the regulatory region of other genes negatively regulated by insulin such as those encoding phosphoenolpyruvate carboxykinase, tyrosine aminotransferase, and insulin-like growth factor-binding protein 1. Fluorescence in situ hybridization analysis revealed that the murine FATP gene is localized to chromosome 8, band 8B3.3. Interestingly, this region of chromosome 8 contains a cluster of three other genes important for fatty acid homeostasis, lipoprotein lipase, the mitochondrial uncoupling protein 1 (UCP1) and sterol regulatory element-binding protein 1. These results characterize the murine FATP gene and its insulin responsiveness as well as present a framework for future studies of its role in lipid metabolism, obesity, and type II diabetes mellitus.
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PMID:Characterization of the murine fatty acid transport protein gene and its insulin response sequence. 976 71

To investigate the cellular mechanisms and cell-cell heterogeneity of the actions of insulin-like growth factor-1 (IGF-1) and follicle-stimulating hormone (FSH) exerted alone and in combination on ovarian cholesterol side-chain cleavage gene expression (P450scc mRNA) in (pig) granulosa cells, we implemented semiquantitative in situ molecular hybridization at the single target-cell level. To this end, a 1-kb cDNA specific to the catalytic region of porcine p450scc gene was subcloned into pGEM-3 and directionally transcribed in vitro in the presence of 35S-dUTP to yield radiolabeled antisense (and sense, negative control) cRNA hybridization probes. Swine granulosa cells harvested nonenzymatically from immature (1-5 mm) Graafian follicles were anchored on eight-chamber multiwell slides and treated with control solvent, human recombinant IGF-1 (10nM), ovine FSH (10nM), or both hormones, for 48 h to stimulate progestin biosynthesis maximally. After appropriate cellular permeabilization, cRNA hybridization, and solvent washes, granulosa cells were exposed to Kodak NTB-2 emulsion for 6 wk. Semiquantitative automated image analysis software (NIH IMAGE 1.5) was used to evaluate the number of silver grains deposited/20,000 square pixels. Specificity controls included labeled sense riboprobe, pretreatment with RNase, and 100-fold molar excess unlabeled cRNA. Grain counts and their distributions were examined by ANOVA and the Wilcoxon nonparametric test. The mean number of silver grains deposited per granulosa cell increased over control (reflecting specific P450scc mRNA expression) in granulosa cells pretreated with IGF-1, FSH, or IGF-1 + FSH (p < 0.05 by ANOVA). The rank order of abundance of expression of P450scc mRNA (grains/ovarian cell) was (IGF-1 + FSH) > FSH > IGF-1 > control treatment. Distributional analysis showed that each treatment introduced skewed distributions toward granulosa cells expressing more P450scc per cell than controls (p < 0.01). The median grain count of granulosa cells treated with FSH was significantly increased over that of IGF-1 treatment (p < 0.05). Treatment with both IGF-1 and FSH further shifted the grain count distribution per cell to favor granulosa cells expressing more P450scc mRNA compared to IGF-1 or FSH treatment alone (p < 0.05). Accordingly, a demonstrable mechanism of IGF-1 and FSH's regulation of specific P450scc gene expression at the single granulosa cell level is amplification in the number of target ovarian cells expressing this enzymatically rate-determining gene transcript. Interestingly, the induction of P450scc mRNA is not sufficient to explain fully the synergistic increases in progesterone accumulation driven by combined treatment with IGF-1 and FSH, thus suggesting that other steroidogenic control points are also targets of IGF-1/FSH action.
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PMID:In situ amplification of the cytochrome P-450 cholesterol side-chain cleavage enzyme mRNA in single porcine granulosa cells by IGF-1 and FSH acting alone or in concert. 979 31

The components of the insulin-like growth factor (IGF) axis have been investigated in the normal human thymus. Using ribonuclease protection assays (RPA), IGF-II transcripts were detected in the normal human thymus. By reverse transcriptase polymerase chain reaction (RT-PCR) analyses, promoters P3 and P4 were found to be active in the transcription of IGF2 gene within human thymic epithelial cells (TEC). No IGF-II mRNA could be detected in human lymphoid Jurkat T cells with 30 cycles of RT-PCR. By Northern blot analyses, IGFBP-2 to -6 (but not IGFBP-1) were found to be expressed in TEC with a predominance of IGFBP-4. Interestingly, Jurkat T cells only express IGFBP-2 but at high levels. The type 1 IGF receptor was detected in Jurkat T cells but not in human TEC. The identification of the components of the IGF axis within separate compartments of the human thymus adds further evidence for a role of this axis in the control of T-cell development. The precise influence of thymic IGF axis upon T-cell differentiation and immunological self-tolerance however needs to be further investigated.
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PMID:Characterization of the insulin-like growth factor axis in the human thymus. 1033 24


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