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

We have reported previously [Sakakibara, et al. (1991) Chem. Pharm. Bull. 39, 146-149] that a protein purified from a partially purified pharmaceutical preparation of human chorionic gonadotropin (a urinary protein preparation from pregnant women) is a unique nonsecretory ribonuclease (RNase)-like protein on the basis of its amino terminal sequence homology. We purified the protein further from the same materials by gel filtration and reversed-phase column chromatographies with RNase activity as an index. The purified protein was designated RNase UpI-2. The catalytic activity and its sensitivity to inhibition by divalent cations suggest that the protein is related to nonsecretory RNase. The estimated molecular weight of RNase UpI-2 (38 kDa) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was significantly higher than that of urinary nonsecretory RNases (13 to 19 kDa) reported so far. After trifluoromethanesulfonic acid treatment, the molecular weight of RNase UpI-2 was reduced and approached that of nonsecretory RNase, which indicated that the protein contains a significant amount of carbohydrate (approximately 50%). RNase UpI-2 was immunoreactive with antibodies to a nonsecretory RNase, RNAase 1 [Yasuda et al. (1988) Biochim. Biophys. Acta 965, 185-194]. By immunoblot analysis of the protein freshly prepared from various urine samples, it was shown that a considerable amount of RNase UpI-2 is present in urine of pregnant women, but only a trace of RNase UpI-2, if any, was detected in urine of nonpregnant women and men. These results suggest the possibility that RNase UpI-2 may have been formed via a specific protein modification in pregnant women.
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PMID:Characterization of a unique nonsecretory ribonuclease from urine of pregnant women. 158 93

Addition of a ribonuclease inhibitor (10 micrograms/ml) from human placenta caused 2-3-fold increase of [3H]leucine incorporation in the wheat germ extract as directed by human placental poly (A)-mRNA. Analysis of the translated products by sodium dodecyl sulfate/polyacrylamide gel electrophoresis/fluorography revealed that the inhibitor preferentially increased the yields of the larger proteins, particularly those of larger than Mr 40 000. In the presence of the inhibitor, yields of two placental proteins (human placental lactogen and human chorionic gonadotropin) were increased about 70-80% as detected by immunoprecipitation with specific homologous antisera. The method provided an improvement of translation system for studying biosynthesis of other human placental proteins.
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PMID:The effect of a ribonuclease inhibitor from human placenta on the in vitro synthesis of human placental proteins. 684 Feb 76

Experiments on white male rats were made to study and compare the action of hormonal drugs (testosterone propionate, retabolil and chorionic gonadotropin) on lysosomal enzymes of different tissues. There were differences in the changes in the activity of acid phosphatase, ribonuclease, cathepsins and beta-galactosidase after a single administration of testosterone and after a course of drug treatment. Retabolil and chorionic gonadotropin acted on lysosomal enzymes of spermatic vesicles similarly to testosterone given in a single dose. As far as the activity of liver cathepsins and beta-galactosidase is concerned retabolil was found to produce an opposite effect as compared to that of testosterone.
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PMID:[Effect of hormonal preparations on lysosome enzyme activity in rat tissues]. 686 93

Eosinophil derived neurotoxin (EDN) is a ubiquitous human ribonuclease, occurring not only in eosinophils, but also in many tissues and body fluids. It may be a contaminant of commercial human urinary preparations of chorionic gonadotropin (hCG) and other glycoprotein hormones. Here we describe the use of a fast commercial assay to quantify this contaminant and demonstrate that the content varies much between different commercial glycoprotein hormone preparations. As this ribonuclease may have a cytotoxic activity on certain cells, it is useful to be able to determine its quantity in a fast and reliable way in these preparations.
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PMID:Eosinophil derived neurotoxin (EDN) levels in commercial human urinary preparations of glycoprotein hormones. 1019 98

RT-PCR analysis demonstrated that bovine conceptuses at days 16, 23 and 30 expressed LH-beta-like and glycoprotein hormone alpha-like transcript sequences; adult kidney, liver and brain produced predominantly unspliced products. Sequencing of the LH-beta-like fragment (from conceptuses at day 30) indicated complete homology with the published sequence. In addition, ribonuclease protection assay of RNA samples from bovine conceptuses at day 30 with a bovine LH-beta probe revealed the presence of protected molecules that appeared to be full length. Northern blot analysis of total RNA from conceptuses at day 30 failed to demonstrate the presence of LH-beta or glycoprotein alpha subunit transcripts, whereas both transcripts were readily detected in adult pituitary RNA. Administration of hCG into the uterus of heifers from day 14 to day 16 of the oestrous cycle did not affect circulating progesterone concentrations, whereas the same dose increased progesterone concentrations (P < 0.05) when administered intravenously. These results indicate that the early bovine conceptus transcribes genes encoding LH-alpha and -beta subunits, but at a level unlikely to be of physiological consequence.
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PMID:Expression of luteinizing hormone genes in bovine conceptuses. 1186 97

Several commercial preparations of human chorionic gonadotropin (hCG) have been tested as therapy for Kaposi's sarcoma (KS) in clinical trials, but with discordant outcomes. We also have found dramatic differences in the cytotoxic effects of four different commercial hCG preparations on an established KS cell line, KSIMM. A co-purified moiety (ies) present in these preparations may explain these differences. The eosinophil-derived neurotoxin ribonuclease, extended with four extra residues ((-4)EDN), has been suggested to be the putative anti-KS compound in the hCG preparations, being specifically recognized by the cells through its N terminal extension. We therefore synthesized a 16-residue peptide (MSLHV-NT12 EDN), made to resemble the active recognition sequence of (-4)EDN. MSLHV-NT12 EDN displays a dose-dependent cytotoxic effect on KSIMM (killing 50% of the cells at 9 microg/ml). The cytotoxic effect is specific for KS cells, MSLHV-NT12 EDN being harmless even at 100 microg/ml for a melanoma cell line (SK-MEL-28) or for normal human fibroblasts. We also demonstrated that MSLHV-NT12 EDN induces apoptosis in KSIMM cells. In conclusion, MSLHV-NT12 EDN is a specific proapoptotic substance for KS cells, which warrants further investigation into its in vivo effects.
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PMID:A synthetic peptide derived from the human eosinophil-derived neurotoxin induces apoptosis in Kaposi's sarcoma cells. 1527 5

We have used the most advanced programs currently available to construct the first three-domain structure of the human thyrotropin receptor (TSHR) using comparative modeling. The model consists of a leucine-rich domain (LRD; amino acids 36-281; porcine ribonuclease inhibitor used as a template for modeling), a cleavage domain (CD; amino acids 282-409; tissue inhibitor of matrix metalloproteinases 2 as template) and transmembrane domain (TMD amino acids 410-699; bovine rhodopsin as template). Models of human, porcine, and bovine TSH were also constructed (human chorionic gonadotropin [hCG] and human follicle stimulating hormone [hFSH] as templates). The LRD has a characteristic horseshoe shape with 10 tandem homologous repeats. The CD consists of beta-barrel and alpha helix structures (OB-like fold) with two disulfide bridges and the structure around these disulfide bridges remains stable after cleavage. The TMD presents the typical seven membrane-spanning helices. The TSH, LRD, CD, and TMD models were brought together in an extensive series of docking experiments. Known features of the TSH-TSHR interaction were used for selection of appropriate complexes that were then validated using a different set of experimental data. A similar approach was used to build a model of a complex between the TSHR and a monoclonal TSHR antibody with weak thyroid stimulating activity. Human thyrotropin (hTSH) alpha chains were found to make contact with many amino acids on the LRD surface and CD surface whereas no interaction between the beta chains and the CD were found. The higher affinity of bovine thyrotropin (bTSH) and porcine thyrotropin (pTSH) (relative to hTSH) for the TSHR is explained well by the models in terms of charge-charge interactions between their alpha chains and the receptor. Experimental observations showing increased sensitivity of the TSHR to hCG after mutation of TSHR Lys209 to Glu are explained well by our model. Furthermore, several mutations in the TMD that are associated with increased TSHR basal activity are predicted from our model to be caused by the formation of new interactions that stabilize the activated form of the TMD.
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PMID:Analysis of the thyrotropin receptor-thyrotropin interaction by comparative modeling. 1617 67

Cholesterol transport is essential for many physiological processes, including steroidogenesis. In steroidogenic cells hormone-induced cholesterol transport is controlled by a protein complex that includes steroidogenic acute regulatory protein (StAR). Star is expressed as 3.5-, 2.8-, and 1.6-kb transcripts that differ only in their 3'-untranslated regions. Because these transcripts share the same promoter, mRNA stability may be involved in their differential regulation and expression. Recently, the identification of natural antisense transcripts (NATs) has added another level of regulation to eukaryotic gene expression. Here we identified a new NAT that is complementary to the spliced Star mRNA sequence. Using 5' and 3' RACE, strand-specific RT-PCR, and ribonuclease protection assays, we demonstrated that Star NAT is expressed in MA-10 Leydig cells and steroidogenic murine tissues. Furthermore, we established that human chorionic gonadotropin stimulates Star NAT expression via cAMP. Our results show that sense-antisense Star RNAs may be coordinately regulated since they are co-expressed in MA-10 cells. Overexpression of Star NAT had a differential effect on the expression of the different Star sense transcripts following cAMP stimulation. Meanwhile, the levels of StAR protein and progesterone production were downregulated in the presence of Star NAT. Our data identify antisense transcription as an additional mechanism involved in the regulation of steroid biosynthesis.
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PMID:Hormone-dependent expression of a steroidogenic acute regulatory protein natural antisense transcript in MA-10 mouse tumor Leydig cells. 2182 56