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)

A solution-hybridization ribonuclease-protection assay was used to identify epidermal growth factor (EGF) mRNA in mouse brain and to compare the regional and developmental levels of EGF gene expression in the CNS with those of its structural homolog, transforming growth factor-alpha (TGF-alpha). Adult brain regions examined included brainstem, cerebellum, cerebral cortex, hippocampus, basal hypothalamus, olfactory bulb, olfactory tubercle, striatum, and thalamus. While both EGF and TGF-alpha mRNAs were detected in all regions, TGF-alpha mRNA levels were 15-170 times higher, ranging from 0.39 (cerebellum and cerebral cortex) to 2.93 (striatum) pg TGF-alpha mRNA/micrograms total cytoplasmic RNA. In contrast, EGF mRNA levels ranged from 11 to 36 fg EGF mRNA/micrograms, with the highest regional concentrations observed in olfactory bulb, basal hypothalamus, and cerebellum. In our comparison between sexes, no significant male-female differences in EGF or TGF-alpha mRNA levels were observed for any region of adult brain. However, in the pituitary gland, consisting of both endocrine and neural elements, EGF and TGF-alpha mRNA levels were significantly higher in males (234 and 215 fg/micrograms, respectively) than in females (172 and 118 fg/micrograms, respectively). An examination of growth factor gene expression in the developing CNS revealed EGF and TGF-alpha mRNAs detectable as early as embryonic day 14 (earliest time point studied). While gene expression for both peptides continued into the postnatal period, EGF and TGF-alpha mRNA levels were nearly equal to adult concentrations by postnatal day 10. Taken together, our findings provide evidence for the synthesis of EGF in brain and suggest a role for both EGF and TGF-alpha in the development and support of the mammalian CNS.
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PMID:Regional distribution and developmental expression of epidermal growth factor and transforming growth factor-alpha mRNA in mouse brain by a quantitative nuclease protection assay. 157 63

Evidence has shown that epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha) and their receptors (EGF receptors) are present in the anterior pituitary, indicating that the growth factors are synthesized in situ and act locally. Studies have demonstrated that EGF could stimulate the hypothalamus-pituitary-adrenal (HPA) cortex axis, particularly at the pituitary level in vivo and in vitro, and also stimulate TGF alpha messenger RNA (mRNA) expression in cultured bovine pituitary cells. Recently, our studies have demonstrated that some stresses up-regulated EGF mRNA expression in the anterior pituitary, as detected by ribonuclease protection assay, further indicating the possible roles of EGF in the stress response. However, little is yet known about the sources and targets (sites of EGF receptors) of the growth factors in the pituitary. Therefore, this study was designed to localize EGF and TGF alpha mRNA and their receptors as well as to assess the effects of cold stress (CS) on their expression in the subsets of pituitary cells. In situ hybridization immunocytochemistry coupled with immunocytochemistry and dual immunocytochemistry studies revealed the presence of 1) EGF mRNA in somatotropes and gonadotropes; 2) TGF alpha mRNA in somatotropes, gonadotropes, and lactotropes; and 3) EGF receptors in all subsets of pituitary cells. CS (30 min) induced the expression of EGF mRNA in corticotropes and thyrotropes. EGF expression was not altered in somatotropes and gonadotropes. No significant changes were detected in TGF alpha mRNA expression in the pituitary cells after 30 min of CS. Expression of EGF receptors was also increased after 30 min of CS. This resulted from increases in EGF receptor-labeled cells among thyrotropes and gonadotropes. The cold stress-induced expression of EGF mRNA in corticotropes and thyrotropes fits with their overall activation after this type of stress. The increase in EGF receptor-labeled cells among thyrotropes may point to an important autocrine role for EGF in maintaining TSH responses to cold. On the other hand, the significance of EGF receptor up-regulation in gonadotropes (FSH-containing cells) caused by CS remains unknown.
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PMID:Epidermal growth factor and transforming growth factor-alpha messenger ribonucleic acids and their receptors in the rat anterior pituitary: localization and regulation. 772 Jun 77

Evidence has shown that epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are present in the anterior pituitary as well as the hypothalamus, and that EGF can influence the function of pituitary cells, particularly corticotropes in vivo and in vitro. However, little is known about their exact functional roles and how they are regulated in these two areas. The present study was designed to determine if EGF and TGF alpha messenger RNA (mRNA) are expressed in the rat anterior pituitary and hypothalamus and how stress conditions such as cold, ether, or restraint affect their local expression. A sensitive mRNA detection method, the ribonuclease protection assay, detected both EGF and TGF alpha mRNA in the rat anterior pituitary and hypothalamus. Reverse transcription-polymerase chain reaction (RT-PCR) further showed the presence of EGF and TGF alpha mRNA in these two areas and several other rat tissues (submandibular gland, liver, kidney, lung cerebral cortex, and testis). No TGF alpha mRNA was found in the kidney, however. EGF mRNA was up-regulated in the anterior pituitary after 30 min acute cold stress (CS) and restrainer-restraint stress (RS) but not 30 min after ether stress (2 min, ES), novelty stress (NS), or tape-restraint stress (TS). Further analysis showed that EGF mRNA expression decreased after 1 h CS (1C) and then increased after 3 h CS (3C). In contrast, TGF alpha mRNA in the anterior pituitary and hypothalamus and hypothalamic EGF mRNA did not show significant changes in response to either acute stresses (CS, ES, RS, TS, NS) or longer CS (1C, 3C). Our results suggest that 1) EGF, is up-regulated after some stresses; 2) increased pituitary EGF mRNA in response to stresses varies with the type of stress; and 3) pituitary TGF alpha and hypothalamic EGF and TGF alpha may be not involved in the stress response.
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PMID:Differential regulation of epidermal growth factor and transforming growth factor-alpha messenger ribonucleic acid in the rat anterior pituitary and hypothalamus induced by stresses. 786 95

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are mitogenic to the intestinal epithelium. To further clarify their role in the developing human fetal gut, their expression was studied in fetuses at 15 to 20 wk of gestation. TGF-alpha mRNA was present throughout the gastrointestinal tract, most abundantly in the duodenum. EGF mRNA could be detected only with ribonuclease protection assay and reverse transcription-polymerase chain reaction analysis. The effect of EGF and TGF-alpha on TGF-alpha mRNA expression was studied by culturing explants of fetal jejunum, ileum, and colon for 7 d in Leibowitz L-15 medium supplemented with 100 micrograms/L of either EGF or TGF-alpha. EGF receptor-like immunoreactivity was detected in both the villi and the crypts. In the jejunum, exogenous EGF up-regulated TGF-alpha mRNA 3-fold. However, exogenous TGF-alpha reduced its own mRNA by 40%. No mature 6-kD TGF-alpha was detected in the culture medium by Western blotting, but precursor forms of approximately 30 and 68 kD were present. The ileum and colon did not respond to either growth factor. Besides the gut, TGF-alpha was expressed in the gallbladder, salivary gland, adrenals, brain, kidney, liver, and placenta. The data imply an important role for TGF-alpha and EGF in the developing intestine.
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PMID:Transforming growth factor-alpha and epidermal growth factor expression in human fetal gastrointestinal tract. 851 Oct 20

Thrombin is one of the first regulatory molecules present at sites of CNS trauma or injury. Exposure of neuronal and glial cells to thrombin produces potent morphological as well as cytoprotective and cytotoxic effects, but little is known about how this important modulator affects neurotransmitter signaling. In astrocyte cultures that have been morphologically differentiated by exposure to transforming growth factor-alpha, addition of thrombin induced a retraction of astrocytic processes and suppressed the stimulation of phosphoinositide hydrolysis by the selective metabotropic glutamate receptor (mGluR) agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid. In addition to the suppression of phosphoinositide hydrolysis, thrombin treatment produced a corresponding reduction in level of mGluR5 mRNA as demonstrated with ribonuclease protection assay and reduced content of mGluR5 receptor protein as seen with western blotting. In contrast, thrombin exposure up-regulated astrocyte beta-actin mRNA levels. A synthetic hexapeptide with a sequence corresponding to the amino-terminus of the thrombin receptor's tethered ligand also mimicked the ability of thrombin to suppress mGluR5 levels and to increase beta-actin mRNA content, suggesting that these effects of thrombin are mediated by proteolytically activated cell surface thrombin receptors. Thrombin's suppressive effect on mGluR5 was resistant to pretreatment with pertussis toxin or various protein kinase and protein phosphatase inhibitors. However, the serine/threonine protein kinase inhibitor H-7 did prevent thrombin-induced reversal of astrocyte stellation and induction of beta-actin mRNA levels, indicating that these effects of thrombin involve a signaling pathway distinct from the one that mediates the suppressive effects of thrombin on mGluR5.
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PMID:Exposure of astrocytes to thrombin reduces levels of the metabotropic glutamate receptor mGluR5. 885 25

The present study was designed to investigate whether heparin-binding epidermal growth factor-like growth factor and its related peptides are expressed in response to gastrin in rat stomach. Rat gastrin-17I (2.5 nmol/kg/hour) or gastrin-17I plus gastrin receptor antagonist, L-740,093 (2.0 mg/kg/hour), was injected intravenously into male Sprague-Dawley rats. RNA was extracted from oxyntic mucosa, and heparin-binding epidermal growth factor-like growth factor and related peptide gene expression was estimated using a ribonuclease protection assay. The level of transforming growth factor-alpha mRNA did not change at any time point during the experiment. In contrast, the levels of heparin-binding epidermal growth factor-like growth factor and amphiregulin mRNA were significantly increased within 3 hours following gastrin infusion and reached maximum levels 6 and 12 hours later, respectively. Continuous infusion of gastrin significantly increased oxyntic mucosal proliferation. Gastrin receptor antagonist significantly inhibited gastrin-induced heparin-binding epidermal growth factor-like growth factor and amphiregulin gene expression and gastrin-induced oxyntic mucosal proliferation. These findings indicate that heparin-binding epidermal growth factor-like growth factor and amphiregulin genes are induced by gastrin and that they play a role in the trophic action of gastrin on oxyntic mucosa.
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PMID:Induction of heparin binding epidermal growth factor-like growth factor and amphiregulin mRNAs by gastrin in the rat stomach. 920 88

The purpose of this study is to evaluate the role of keratinocyte growth factor (KGF), transforming growth factor-alpha (TGF-alpha), and their receptors in altered renal growth caused by complete ureteral obstruction in the developing kidney. Neonatal and adult rats underwent complete unilateral ureteral ligation or sham operation. The kidneys were harvested at 1, 5, 10, 20, and 30 days after obstruction. Renal growth and development was assessed by histology and immunohistocytochemical localization of vimentin, cytokeratin and smooth muscle-alpha actin. Cellular proliferation was measured by [3H]thymidine labeling index of all cells. RNase protection assays were used to quantify mRNA encoding for KGF, KGF receptor, TGF-alpha, and epidermal growth factor (EGF) receptor. Ureteral obstruction in the developing kidneys resulted in decreased DNA synthesis, rapid parenchymal loss, myofibroblast proliferation in the interstitium, decreased tubular epithelial cells formation, and development of cystic dysplasia. In comparison, obstruction in the mature kidneys resulted in transient growth in the medullary ductal cells, parenchymal loss, and myofibroblast proliferation at a later time, lymphocytic infiltration in the interstitium but not cystic dysplasia. KGF and KGF receptor mRNA levels were increased in obstructed neonatal kidneys. Similarly, TGF-alpha and EGF receptor mRNA levels were increased. Delayed and more moderate increases in KGF, KGF receptor, and TGF-alpha expression were also seen in the obstructed mature kidneys. Of importance, the amount of EGF receptor mRNA was not increased in the obstructed compared with the contralateral or sham-operated adult kidneys. This study suggests that obstruction alters the normal expression pattern of KGF, TGF-alpha, and their receptors in renal development. These changes may be responsible for the impaired renal growth and altered development seen in ureteral obstruction of the kidneys. Although some changes are similar to those seen in the adult kidney, the increased expression of TGF-alpha and cystic dysplasia are unique to neonatal obstruction.
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PMID:Growth factor expression in the obstructed developing and mature rat kidney. 1006 5

Proto-oncogenes are involved in the regulation of gene expression, for example after ligand binding to growth factor receptors. Expression of the proto-oncogenes c-fos, c-jun, c-ha-ras and c-myc was studied in in vivo grown and in vitro cultured bovine preimplantation blastocysts employing RT-PCR, ribonuclease protection assay and immunohistochemistry. Thirteen- and 14- day-old preimplantation blastocysts, i.e. stages before and during trophoblast elongation, were used. In in vivo-grown blastocysts c-fos, c-jun and c-ha-ras transcripts as well as c-Fos, c-Jun and c-Myc proteins were detected in all stages studied. Cultured blastocysts were treated with 10 nM epidermal growth factor and 10 nM transforming growth factor-alpha simultaneously. Epidermal growth factor and transforming growth factor-alpha treatment induced c-fos mRNA and c-Myc protein expression. The induction of downstream targets of the epidermal growth factor receptor by epidermal growth factor and transforming growth factor-alpha indicates a functional epidermal growth factor signal transduction pathway in elongating bovine blastocysts.
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PMID:Expression of proto-oncogenes in bovine preimplantation blastocysts. 1083 31

This study examined whether changes in the levels of the messenger RNAs (mRNAs) encoding the gamma-aminobutyric acid (GABA) synthesizing enzymes, glutamate decarboxylase (GAD)65 and GAD67 and transforming growth factor-alpha (TGFalpha) in the hypothalamus are correlated with the arrest of pulsatile GnRH release during infancy in the agonadal male monkey. This experiment also provided the opportunity to examine changes in hypothalamic GnRH gene expression during this critical phase of primate development. Male rhesus monkeys were castrated at 1 week of age: four were killed 4-7 weeks after orchidectomy while pulsatile GnRH release was robust as reflected by high circulating LH levels, and four were killed at 12-15 months of age after establishing that pulsatile GnRH release had been arrested. GAD65, GAD67, TGFalpha, and GnRH mRNA levels were estimated using RNase protection assays employing homologous probes and the results were expressed relative to cyclophilin mRNA levels. GnRH peptide was measured by RIA. GAD65 and GAD67 mRNA levels in the hypothalamus of juveniles were significantly greater than those in neonatal monkeys. On the other hand, hypothalamic TGFalpha and GnRH mRNA (and peptide) levels in agonadal neonate and juvenile monkeys were indistinguishable. These results indicate that the molecular concomitants associated with bringing the hypothalamic GnRH pulse generator into check in agonadal neonatal males are not a mirror image of those previously reported at the time this neuronal network is reactivated at puberty when TGFalpha and GnRH gene expression increase and GAD65 and GAD67 mRNA levels remain unchanged. Thus, the neurobiological mechanism that reactivates pulsatile GnRH release at puberty is likely to involve more than a simple reversal of that underlying inhibition of the same network in late infancy.
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PMID:Changes in hypothalamic gene expression associated with the arrest of pulsatile gonadotropin-releasing hormone release during infancy in the agonadal male rhesus monkey (Macaca mulatta). 1096 98