Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Restriction of dietary protein consumption of young male rats results in decreased growth velocity and a reduction in the abundance of hepatic IGF-I mRNA. It is not known whether the reduction of IGF-I mRNA abundance in the liver of protein-restricted rats results from a decrease in IGF-I gene transcription. In the present study, three experiments were performed with 4-week-old male rats to examine the effect of protein restriction on IGF-I gene transcription in liver. In these experiments, we monitored IGF-I nuclear transcripts (pre-mRNA) within total cellular RNA using a ribonuclease protection assay. In the first experiment, a consistent decrease in IGF-I mRNA from animals fed isocaloric diets containing 20% (control), 12%, 8% and 4% protein (dietary effect, P < 0.001) was not paralleled by a decrease (P > 0.50) in IGF-I pre-mRNA. Two additional experiments examining the effect of 4% vs 20% protein diets yielded comparable results. Pooled results from these two studies (n = 12/treatment) demonstrated that a 64% reduction (P < 0.0001) in IGF-I mRNA abundance was not accompanied by a decrease in IGF-I pre-mRNA (1.17 vs 1.31 +/- 0.21 image density units for 4% and 20% protein treatments). Unlike IGF-I, the abundance of carbamyl phosphate synthetase-I (CPS-I) pre-mRNA and mRNA was comparably reduced (approximately 70%, P < 0.001), indicating that the decrease in mRNA of this urea cycle enzyme during protein restriction occurs predominantly by a transcriptional mechanism. A common feature of all experiments was a pronounced variability in the expression of hepatic IGF-I pre-mRNA among animals, which was not diet specific. To test whether the variability in IGF-I gene transcription was correlated with variability in the transcription of another gene that is regulated by GH, we quantified the abundance of nuclear transcripts for the serine protease inhibitor 2.1 (SPI 2.1) gene. A positive association (r = 0.81, P < 0.0001) between SPI 2.1 and IGF-I nuclear transcripts was demonstrated. The correlation between IGF-I and SPI 2.1 transcripts was specific, because the quantity of IGF-I and CPS-I nuclear transcripts was not correlated in this study. Although transcription of the IGF-I and SPI 2.1 genes was similar, the abundance of SPI 2.1 mRNA was not altered by protein deprivation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:IGF-I and serine protease inhibitor 2.1 nuclear transcript abundance in rat liver during protein restriction. 763 24

Glucocorticoids have a number of effects on bone cell function, some of which might be mediated by changes in the synthesis or activity of insulin-like growth factors (IGFs). Glucocorticoids inhibit IGF-I, but not IGF-II, synthesis in osteoblasts and decrease the expression of selected IGF-binding proteins. The effects of glucocorticoids on IGF-I and -II receptor messenger RNA (mRNA) expression in osteoblasts are not known, and changes in IGF-I or -II receptor levels could result in changes in IGF activity. We examined the effects of glucocorticoids on IGF-I and -II receptor mRNA expression in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). Cortisol at 1 microM for 2-48 h did not alter IGF-I receptor transcripts, as determined by Northern blot analysis and ribonuclease protection assay. In contrast, cortisol caused a time- and dose-dependent inhibition of IGF-II receptor mRNA levels. The effect was maximal at 0.1-1 microM for 24-48 h and was accompanied by a decrease in IGF-II receptor levels, as determined by affinity labeling, cross-linking and polyacrylamide gel electrophoresis, Western immunoblot, and Scatchard analysis. The effect of cortisol on IGF-II receptor transcripts was not dependent on de novo protein synthesis. Cortisol did not modify the IGF-II receptor mRNA half-life in transcriptionally arrested Ob cells and decreased the rate of IGF-II receptor RNA transcription in nuclear run-on assays. In conclusion, cortisol decreases transcription of the IGF-II receptor in Ob cell cultures, an effect that could mediate selected actions of glucocorticoids in bone.
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PMID:Cortisol represses insulin-like growth factor II receptor transcription in skeletal cell cultures. 766 43

Abnormalities of GH secretion and clearance are well-documented in poorly controlled insulin-dependent diabetes mellitus (IDDM), but the contribution of the receptor (GHR) and the GH-binding protein (GHBP) to these abnormalities has not been defined. We studied the expression of the GHR/GHBP gene in the livers, hearts and kidneys in streptozocin-induced diabetes (STZ-D) in the rat. GHR and GHBP mRNA levels were measured by Northern blot and ribonuclease protection assays. Whereas levels of GHR and GHBP mRNA were significantly decreased in liver and heart of STZ-D rats when compared with the control group (P < 0.01), GHR mRNA was significantly increased in the kidneys of STZ-D rats (P = 0.03). Six days of insulin treatment did not significantly alter the levels of GHR/GHBP mRNA in the liver or heart of STZ-D rats, but significantly decreased GHBP mRNA (P = 0.04) in the kidney. Circulating IGF-I was reduced, as was IGF-I mRNA in the liver and heart of STZ-D rats; only circulating IGF-I was restored by insulin treatment. Neither STZ-D nor insulin treatment affected IGF-I or IGF-I receptor mRNA concentrations in the kidney. We conclude that (1) STZ-D modulates the expression of the GHR/GHBP gene and (2) that these changes in GHR/GHBP mRNA concentrations are tissue-specific; STZ-D decreases GHR/GHBP mRNA in liver and heart tissue but increases GHR mRNA concentrations in the kidney. Our results indicate a role for decreased numbers of hepatic GHRs in the pathogenesis of resistance to GH's actions in terms of IGF-I generation and promotion of linear growth in IDDM. We postulate that increased GHR expression in the kidney may be involved in the renal complications of IDDM.
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PMID:Tissue-specific regulation of the growth hormone receptor gene in streptozocin-induced diabetes in the rat. 796 96

During the menstrual cycle, the endometrium undergoes characteristic changes in response to circulating sex steroids. Intense mitotic activity of glands and stroma occurs in the proliferative (estradiol-dominant) phase, and glandular secretion and stromal differentiation in the secretory (progesterone-dominant) phase. The insulin-like growth factors (IGF-I and IGF-II) promote cellular growth and differentiation and have been proposed to participate in these cyclic endometrial events, acting as mediators of steroid hormones. The objective of this study was to determine whether the messenger RNAs (mRNAs) encoding the IGF peptides and the type I and type II IGF receptors are differentially expressed in human endometrium during the menstrual cycle and in early pregnancy. A solution hybridization ribonuclease protection assay, using 32P-labeled riboprobes for IGF-I, IGF-II, and beta-actin (control), revealed IGF-I gene expression primarily in proliferative and early secretory endometrium and abundant IGF-II gene expression in mid-late secretory endometrium and early pregnancy decidua. Northern analysis, using IGF-I and IGF-II complementary DNA probes, revealed multiple IGF-I mRNAs [2-7.6 kilobase (kb)], expressed primarily in proliferative and early secretory endometrium, and IGF-II mRNAs (1.4-6.0 kb), expressed primarily in secretory endometrium and in early pregnancy decidua. The 7.6-kb IGF-I mRNA and the 6.0-kb IGF-II mRNA were most abundantly expressed. IGF-IEa and IGF-IEb mRNA splicing variants were present in a ratio of about 9:1, respectively. Type I and type II IGF receptor gene expression in endometrium was investigated using specific riboprobes and the ribonuclease protection assay. Messenger RNAs encoding both receptors were more abundantly expressed in the secretory phase and during early pregnancy, compared to the proliferative phase. These results show that mRNAs encoding the IGF peptides and their receptors are differentially expressed in human endometrium, depending on the steroid hormone milieu. The preferential expression of IGF-I mRNA in the proliferative phase supports the hypothesis that IGF-I is an estromedin in human endometrium. The expression of endometrial IGF-II mRNA in the mid to late secretory phase and in early pregnancy supports a role for IGF-II in differentiative functions of the endometrium, perhaps including endometrial tissue shedding in the menstrual cycle or remodeling during early pregnancy.
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PMID:Differential expression of messenger ribonucleic acids encoding insulin-like growth factors and their receptors in human uterine endometrium and decidua. 849

Recent studies have shown that homologues of the mammalian IGF-I and -II genes are also found in teleosts. We report here the cDNAs coding for IGF-I and IGF-II cloned from the gilthead seabream, Sparus aura ta. Sequence comparisons revealed that both IGFs have been well conserved among teleosts, although Sparus IGF-I is shorter bv three amino acid residues due to truncated B-and C-domains. Using the cloned cDNAs as probes, the relative expression of IGF-I and IGF-II mRNAs were assayed in different Sparus tissues. Sparus liver clearly contained the highest level of IGF-I mRNA while relatively high levels of IGF-II mRNA were found in liver, heart and gill using the ribonuclease protection assay. After GH administration the amount of IGF-I mRNA was increased by 220% in liver but no changes in IGF-II mRNA levels were detected in any tissue. We also assayed the expression of IGF-I and IGF-II in Sparus during early development. The IGF-II mRNA level was highest in larva I day after hatching and decreased thereafter. In contrast, IGF-I mRNA was detected in 1-day-old larva but there was an increase in expression in 12- and 16-day-old larva. These results demonstrated that the expression of IGF-I and IGF-II is highly regulated in teleosts and suggest that they play distinct roles during growth and development.
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PMID:Developmental and tissue-regulated expression of IGF-I and IGF-II mRNAs in Sparus aurata. 915 15

A precise role for insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and IGF-receptors (IGF-Rs) in damaged central nervous system (CNS) tissue has not been elucidated, although their expression in the ischemic brain has been demonstrated. However, little is known of IGF responses after CNS trauma. In this study, we have used ribonuclease protection assay, in situ hybridization, and immunohistochemistry to demonstrate that IGF-I, IGFBPs, and IGF-1R expression alters in response to a penetrating CNS injury. Within penetrant cerebral wounds in the acute phase of the response (1-7 days post lesion; dpl), increased levels of IGF-I, IGFBP-1, -2, -3, -6, and IGF-1R protein were localized to injury responsive astrocytes, neurons and cells of the monocyte lineage. IGF-I, IGFBP-2, and 3 showed a congruency in sites of messenger RNA (mRNA) and peptide expression, with IGF-I and IGFBP-2 mRNA expression predominating. IGF-I, IGFBP-1, and IGFBP-3 protein were also associated with the microvascular endothelium, which was accompanied by increased levels of IGFBP-3 mRNA. These early changes in IGFBP expression probably facilitate IGF-I action. Later in the wounding response (7-14 dpl), the expression of IGFBP-4 and IGFBP-5 peaked within astrocytes and neurons, with IGFBP-5 mRNA being specifically localized to the glia limitans within the wound, suggesting an inhibitory role for these proteins, down-regulating the effects of IGF-I chronically. Our evidence suggests that within penetrating CNS wounds, IGF-I acts in an autocrine/paracrine manner to regulate cellular responses, with its spatial and temporal availability being modulated by the differential presence of stimulatory vs. inhibitory IGFBPs.
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PMID:Spatial and temporal changes in the insulin-like growth factor (IGF) axis indicate autocrine/paracrine actions of IGF-I within wounds of the rat brain. 920 48

Five days of treadmill training in rats leads to increased muscle size and running time. This was used to examine the effect of exercise on circulating insulin-like growth factor I [IGF-I; radioimmunoassay (RIA)], local muscle (hindlimb) IGF-I (by RIA), and muscle IGF-I mRNA (by ribonuclease protection assay). Eight-week-old female Sprague-Dawley rats were divided into three groups: control (n = 10); single-exercise test (n = 10), untrained but with one maximal exercise test at the end of the study; and training (n = 16), trained for 5 days and one maximal exercise test on day 6. There were no differences among the groups with respect to circulating IGF-I. Muscle IGF-I protein in trained rats (4.2 +/- 1.5 ng/g of muscle tissue) was significantly greater than both control (0.27 +/- 0.1 ng/g) and single-exercise test (0.62 +/- 0.19 ng/g, P < 0.05 by analysis of variance). There was no difference among the groups in IGF-I mRNA gene expression. These data suggest that there is an early, marked, local muscle increase in IGF-I protein in response to exercise. This increase, however, may not be related to increased muscle IGF-I gene expression. Moreover, the IGF-I response was probably local in nature since it was not matched by any increase in circulating IGF-I.
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PMID:Increase in muscle IGF-I protein but not IGF-I mRNA after 5 days of endurance training in young rats. 936 24

Fetal growth is increased when pregnant gilts are treated with recombinant porcine somatotropin. The mechanism for increased fetal growth was examined by measuring the expression of IGF-I and -II and IGF-binding protein-2 (IGFBP-2) mRNA in liver and reproductive tissues of somatotropin- and saline-treated pregnant gilts. Twenty-four pregnant gilts received daily injections of either saline (control; n=12) or 5 mg recombinant porcine somatotropin (n=12) from day 30 to day 43 of gestation. Gilts were slaughtered on day 44 of gestation and liver, ovary, placenta, placental uterus (uterus with adjacent placental tissue) and non-placental uterus (region of the necrotic tip) were collected. The mRNAs for somatotropin receptor, IGFs -I and -II, IGFBP-2 and pregnancy-associated glycoprotein (a marker of trophoblast tissue) were analyzed by Northern blotting or ribonuclease protection assay. Gilts treated with somatotropin had heavier fetuses and placentas. The concentration of mRNA for the components of the IGF system was tissue-dependent. The uterine IGF-I mRNA concentration was greater in non-placental than in placental uterus. The greatest IGF-II mRNA concentration was observed in placenta, and adjacent uterine tissue expressed IGFBP-2 mRNA intensely. In non-placental uterus, IGFBP-2 mRNA was nearly undetectable. Somatotropin-dependent regulation of IGF-I was only observed in liver, where the greatest somatotropin receptor mRNA concentration was found. In the pregnant uterus, somatotropin failed to change the concentration of IGF or IGFBP-2 mRNA. Pregnancy-associated glycoprotein mRNA concentration was decreased by somatotropin. In summary, increased fetal growth in somatotropin-treated pregnant pigs was not associated with changes in IGF or IGFBP-2 mRNA concentration in reproductive tissues. Other mechanisms, therefore, lead to enhanced fetal growth in somatotropin-treated pregnant pigs.
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PMID:Insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein-2 and pregnancy-associated glycoprotein mRNA in pigs with somatotropin-enhanced fetal growth. 983 61

Although expression of the IGF-II has been demonstrated within the central nervous system (CNS), past studies have failed to reveal its precise roles or responses subsequent to a traumatic injury. To demonstrate that IGF-II, IGFBP, and IGF receptor (-R) expression alters in response to a penetrating CNS injury, we used the techniques of ribonuclease protection assay, in situ hybridization, immunohistochemistry, Western blotting, and RIA. Under normal physiology, IGF-II expression is restricted to the mesenchymal support structures of the brain, including the choroid plexus, where its expression is coincident with that of IGFBP-2. Between 1-7 days post lesion (dpl), in the acute phase following a penetrant wound to the CNS, IGF-II and IGF-IIR protein, but not messenger RNA, were colocalized, with IGF-I, IGF-IR, and IGFBP-1, -2, -3, and -6, to neurons, macrophages, astrocytes, and microglia within the damaged tissue. Within the cerebrospinal fluid (CSF), levels of IGF-II peptide increased to peak at 7 dpl. IGFBP-2, -3, and -6 were also observed within the CSF, with IGFBP-2 predominating and exhibiting an increase in binding efficiency from 7-10 dpl. In the chronic phase of injury (7-14 dpl), an increase in both IGF-II, IGF-IIR and IGFBP-5 messenger RNA and protein was observed specifically and focally in the marginal astrocytes forming the limiting glial membrane of the wound. Thus, our evidence suggests that there are two mechanisms of action for IGF-II within the injured rat brain. During the acute phase, the secretion of IGF-II from the choroid plexus into the CSF is up-regulated, resulting in increased transport of the peptide to the wound. In the CSF, transported IGF-II is complexed to IGFBP-2 and essentially demonstrates an endocrine mode of action with a balance of locally produced IGFBPs modulating its bioactivity in the wound. Later in the wounding response, levels of IGF-II decline in the CSF and the wound neuropil, possibly with the aid of increased IGFBP-5 levels that may help to locally sequester and down-regulate IGF-II activity. Hence, in the chronic phase of the injury response, IGF-II reasserts itself to a predominantly autocrine/paracrine role restricted to the mesenchymal support structures, including the glia limitans, which may help reestablish and maintain tissue homeostasis.
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PMID:Distinct sites of insulin-like growth factor (IGF)-II expression and localization in lesioned rat brain: possible roles of IGF binding proteins (IGFBPs) in the mediation of IGF-II activity. 988 65

Paracrine and autocrine actions of the insulin-like growth factors (IGFs) are inferred by local expression within the bowel. CCD-18Co cells, IEC-6 cells, and immunoneutralization were used to analyze whether IGFs have direct autocrine or paracrine effects on proliferation of cultured intestinal fibroblasts and epithelial cells. Growth factor expression was analyzed by ribonuclease protection assay and RT-PCR. Extracellular matrix (ECM) was analyzed for effects on cell proliferation. CCD-18Co cells express IGF-II mRNAs and low levels of IGF-I mRNA. Conditioned medium from CCD-18Co cells (CCD-CM) stimulated proliferation of IEC-6 and CCD-18Co cells. Neutralization of IGF immunoreactivity in CCD-CM reduced but did not abolish this effect. RT-PCR and immunoneutralization demonstrated that other growth factors contribute to mitogenic activity of CCD-CM. Preincubation of CCD-CM with ECM prepared from IEC-6 or CCD-18Co cells reduced its mitogenic activity. ECM from CCD-18Co cells enhanced growth factor-dependent proliferation of IEC-6 cells. IEC-6 cell ECM inhibited IGF-I action on CCD-18Co cells. We conclude that IGF-II is a potent autocrine mitogen for intestinal fibroblasts. IGF-II interacts with other fibroblast-derived growth factors and ECM to stimulate proliferation of intestinal epithelial cells in a paracrine manner.
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PMID:Autocrine and paracrine actions of intestinal fibroblast-derived insulin-like growth factors. 1019 23


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