Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to obtain a virus-like particle vaccine both for porcine parvovirus (PPV) prevention and growth-promotion, VP2 gene of PPV NJ-a strain was amplified with PCR, and four copies of synthetic somatostatin gene were fused to the N-terminal of VP2 gene. The fused gene was cloned into pFast-HT A to construct the recombinant plasmid pFast-SS4-VP2, then the pFast-SS4-VP2 was transformed into DH10Bac competent cells and recombined with shuttle vector Bacmid, followed by identification with blue-white screening and PCR analysis for three cycles, and the positive recombinant was named as rBacmid-SS4-VP2. The positive Sf-9 cells were transfected with rBacmid-SS4-VP2 by Lipofectamine to produce recombinant baculovirus. When the cytopathic effect (CPE) was obvious, the transfected Sf-9 cell was harvested, and the positive recombinant virus was named as rBac-SS4-VP2. The insertion for the target gene into baculovirus genome was confirmed with PCR. SDS-PAGE and Western blotting revealed that the calculated protein of approximately 68 kDa was in the expressed in the insect cells. The Sf-9 cells infected with rBac-SS4-VP2 were stained positive against PPV antibody using the indirect immunofluorescence assay (IFA). Moreover, the virus particle self-assembly was observed under electron microscopy. 90 four-week-old mice were immunized by the recombinant protein coupled with different adjuvants alhydrogel, IMS and oil. VP2-specific ELISA antibodies, PPV-specific neutralizing antibody, somatostatin antibody and growth hormone levels were examined to evaluate the immunogenicity of this virus like particle. Results indicated that mice groups immunized rSS4-VP2 protein with alhydrogel and IMS developed similar humoral immune response comparing with inactived PPV vaccine. Mice group immunized with rSS4-VP2 generated higher level of SS antibody and growth hormone comparing with negative control, mice receiving rSS4-VP2 with alhydrogel developed the highest antibody titre than all other groups, while the oil group developed the lowest antibody level. This study provides not only a new rout for production of safe and effective virus like particle subunit vaccine, but also the foundations for peptide presentation and multivalent subunit vaccine design.
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PMID:[Construction and immunogenicity of recombinant porcine parvovirus-like particles with somatostatin]. 2109 Jan 9

Brain derived neurotrophic factor (BDNF) increases the levels of somatostatin (SS) and its mRNA. To test the hypothesis that the regulation of SS synthesis by BDNF occurs at the transcriptional level and requires specific promoter sequences, cerebrocortical and PC12trkB neurons were transiently transfected with different constructs of the SS promoter fused to the luciferase and CAT reporter genes. We demonstrated that BDNF triggered the transcription of the SS gene through the CRE sequence located in the SS promoter. BDNF and SS are genes regulated by K(+)-induced neuronal activity. Using BDNF blocking antibodies, we investigated whether K(+)-induced BDNF was required for K(+)-dependent SS mRNA induction. We found that K(+)-induced SS mRNA was partially prevented when BDNF was blocked. This finding indicated that BDNF mediated the induction of SS mRNA by K(+) depolarization. To identify the mechanisms by which BDNF activates SS gene transcription we first elucidated the signaling pathways activated by BDNF in cerebrocortical cells. We confirmed that BDNF activates the MAPK/ERKs and PI3K/Akt pathways. Both signaling pathways are, in turn, implicated in the activation of CREB by BDNF. In addition we observed that the PKA inhibitors, H89 and Rp-cAMPS decreased BDNF-induced CREB activation. These findings suggested that BDNF-induced CREB activation was also mediated by the cAMP/PKA pathway. We next elucidated the mechanism by which BDNF induces SS mRNA. We observed that H89, PD0998059, KN62 and LY294002 diminished BDNF-induced SS mRNA suggesting that BDNF-induced SS mRNA is mediated by the activation of cAMP/PKA, MAPK/ERKs, CaMK and PI3K pathways.
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PMID:Regulation of somatostatin gene expression by brain derived neurotrophic factor in fetal rat cerebrocortical cells. 2118 49

Somatostatin (SST) is a peptide neurotransmitter/hormone found in several mammalian tissue types. Apart from its natural importance, labeled SST/analogues are utilized in clinical applications such as targeting/diagnosis of neuroendocrine tumors. We report on the development and characterization of a novel, recombinant, fluorescent somatostatin analogue that has potential to elucidate somatostatin-activated cell signaling. SST was genetically fused with a monomeric-red fluorescent protein (mRFP) as the fluorescent label. The attachment of SST to mRFP had no detectable effect on its fluorescent properties. This analogue's potency to activate the endogenous and transfected somatostatin receptors was characterized using assays of membrane potential and Ca(2+) mobilization and immunocytochemistry. SST-mRFP was found to be an effective somatostatin receptor agonist, able to trigger the membrane hyperpolarization, mobilization of the intracellular Ca(2+) and receptor-ligand internalization in cells expressing somatostatin receptors. This complex represents a novel optical reporter due to its red emission spectral band suitable for in vivo imaging and tracking of the somatostatin receptor signaling pathways, affording higher resolution and sensitivity than those of the state-of-the-art radiolabeling bioassays.
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PMID:Pharmacological characterization of a recombinant, fluorescent somatostatin receptor agonist. 2182 34

Our aim was to evaluate the different clinical value of (111)In-pentetreotide hybrid SPET/CT versus SPET alone in detecting carcinoid tumours located in the thoracic and abdominal region. Twenty-four patients with carcinoid tumours histologically proven (13 of abdominal origin, 11 of thoracic origin) underwent (111)In-pentetreotide SPET/CT with hybrid system (Millennium VG with Hawkeye, G.E.M.S., USA) composed of a dual head gamma camera equipped with a low dose X-ray tube. Single photon emission tomography images were performed 4h and 24h after (111)In-pentetreotide intravenous administration, while SPET/CT co-registered images were performed at 4h. Scintigraphic images were first evaluated alone and then re-interpreted by adding transmission fused data. Nine of the 13 patients with tumours of abdominal origin showed pathological SPET images, while 4/13 were negative. Seven out of the 11 patients with tumour of thoracic origin had pathological SPET findings, while 4/11 were negative. In all, 11/24 subjects disclosed abdominal pathological uptake and 10/24 thoracic. In 6/11 abdominal cases SPET/CT allowed anatomical localization of lesions, while in 2/10 in thoracic cases. Additional data were provided by SPET/CT in 8/24 cases (6 abdominal, 2 thoracic), by transmission images characterized as lesions not expressing somatostatin receptors. Sensitivity of SPET alone in all carcinoids was 72%, negative predictive value (NPV) was 50% and accuracy was 78%. Considering abdominal lesions (independently of the origin) sensitivity of SPET alone was 64.7%, NPV was 40%, accuracy was 71.4%. For thoracic lesions sensitivity of SPET alone was 83.3%, NPV was 66.7% and accuracy was 87.5%. For SPET/CT considering together all carcinoids and also separately lesions of abdominal and of thoracic origin, sensitivity, NPV and accuracy were always 100%. In conclusion, SPET/CT imaging was more useful to anatomically detect carcinoids either in abdomen or in thorax and specifically lesions not expressing somatostatin receptors, as compared to SPET alone.
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PMID:(111)In-pentetreotide SPET/CT in carcinoid tumours: is the role of hybrid systems advantageous in abdominal or thoracic lesions? 2208 49

Female BALB/c mice were actively immunized subcutaneously with a recombinant protein of granulocyte-macrophage colony-stimulating factor (GM-CSF) fused with somatostatin (SS) (GM-CSF/SS). Fifty-four days after the primary immunization, the body weight of the immunized mice increased by 4.62% compared with the control (P < 0.05), together with the induction of detectable serum antibodies against SS. The level of serum growth hormone (GH) elevated by 44.54% (P < 0.05) and the mRNA expression of muscular IGF-1 increased by 94% for the GM-CSF/SS-treated mice. The results indicated that the recombinant protein GM-CSF/SS was efficient in inducing specific immunity against SS, subsequently leading to the increase of the GH level by SS neutralization, and ultimately improving the growth of mice.
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PMID:Effect of active immunization against a recombinant mouse granulocyte-macrophage colony-stimulating factor/somatostatin fusion protein on the growth of mice. 2230 89

Somatostatin (SS) is a hormone that inhibits the secretion of growth hormone. Immunization against SS can promote the growth of animals. A novel SS-VP22 fused vaccine, pEGS2SS-V, was constructed from pEGS2SS plasmid with a VP22 gene fragment. Two times of immunization with pEGS2SS-V-induced anti-SS antibodies in mice. Compared with mice immunized with pEGS2SS and 0.85% saline, the growth performance of mice immunized with pEGS2SS-V was increased by 14.1% (P < 0.05) and 48.4% (P < 0.01) on the 2nd week after the first vaccination, respectively. The results indicated that the effects of the somatostatin DNA vaccine could be improved effectively by VP22 gene adjuvant.
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PMID:Evaluation of the VP22 gene adjuvant for enhancement of DNA vaccine against somatostatin in mice. 2244 7

In order to obtain a virus-like particles (VLPs) vaccine both for porcine circovirus type 2 (PCV2) prevention and growth-promotion, somatostatin (SS) gene was fused to the 3'-terminal of ORF2 gene of PCV2 with PCR, and a recombinant baculovirus (rAc-Cap-SS) was constructed. The expression of fusion protein Cap-SS (rCap-SS) with molecular weight of approximately 32kDa was identified by Western blot and indirect immunofluorescence assay in Sf9 cells. The self-assembled VLPs were observed under electron microscopy, which being morphologically similar to the recombinant Cap protein (rCap) expressed in the same baculovirus expressing system. Ninety four-week-old mice were immunized with the recombinant proteins twice. The results showed that mice immunized with rCap-SS protein developed antibody against Cap, which levels being similar to those immunized with rCap protein. The body weight gain and anti-SS antibody in rCap-SS group was higher than those of rCap and negative control groups during 28 and 42 days post inoculation (dpi). Furthermore, twenty 28-day-old piglets were vaccinated twice subcutaneously with the recombinant proteins. The results indicated that PCV2-specific antibody could be induced after vaccination with rCap-SS or rCap protein. Anti-SS antibody could be induced after rCap-SS vaccination and was higher than other groups at 14 and 28 dpi. The level of somatostatin concentration in the blood of pigs in rCap-SS group was significantly decreased at 14 dpi than other groups (P<0.05). The relative daily weight gain (RDWG) of pigs in rCap-SS group was obviously higher than that in other groups at 28 dpi. After challenge with PCV2, pigs in the vaccinated groups had no clearly clinical signs, and the RDWG was significantly higher than that in the challenge control group (CC) (P<0.05). The pathological lesions, viremia and viral load presented in the vaccinated groups were milder than those in challenge control group. It suggested that the recombinant porcine circovirus-like particles displaying somatostatin might be a novel subunit vaccine candidate for preventing PMWS and promoting pig growth.
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PMID:Construction and immunogenicity of recombinant porcine circovirus-like particles displaying somatostatin. 2329 58

Somatostatin is a natural inhibitor of growth hormone, and its analogues are clinically used for the therapy of acromegaly, gigantism, thyrotropinoma, and other carcinoid syndrome. However, natural somatostatin is limited for clinical usage because of its short half-life in vivo. Albumin fusion technology was used to construct long-acting fusion proteins, and Pichia pastoris was used as an expression system. Three fusion proteins, (somatostatin (SS)14)2-human serum albumin (HSA), (SS14)3-HSA, and HSA-(SS14)3, were constructed with different fusion copies of somatostatin-14 and fusion orientations. The expression level of (SS14)3-HSA and HSA-(SS14)3 was much lower than (SS14)2-HSA due to the additional fusion of the somatostatin-14 molecule. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry revealed that severe degradation occurred in the fermentation process. Similar to the standard of somatostatin-14, all three fusion proteins were able to inhibit growth hormone secretion in the blood, with (SS14)2-HSA being the most effective one. On the whole, (SS14)2-HSA was the most effective protein in both production level and bioactivity, and increasing the number of small protein copies fused to HSA may not be a suitable method to improve the protein bioactivity.
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PMID:The effect of albumin fusion patterns on the production and bioactivity of the somatostatin-14 fusion protein in Pichia pastoris. 2371 94

Axonal sprouting of excitatory neurons is frequently observed in temporal lobe epilepsy, but the extent to which inhibitory interneurons undergo similar axonal reorganization remains unclear. The goal of this study was to determine whether somatostatin (SOM)-expressing neurons in stratum (s.) oriens of the hippocampus exhibit axonal sprouting beyond their normal territory and innervate granule cells of the dentate gyrus in a pilocarpine model of epilepsy. To obtain selective labeling of SOM-expressing neurons in s. oriens, a Cre recombinase-dependent construct for channelrhodopsin2 fused to enhanced yellow fluorescent protein (ChR2-eYFP) was virally delivered to this region in SOM-Cre mice. In control mice, labeled axons were restricted primarily to s. lacunosum-moleculare. However, in pilocarpine-treated animals, a rich plexus of ChR2-eYFP-labeled fibers and boutons extended into the dentate molecular layer. Electron microscopy with immunogold labeling demonstrated labeled axon terminals that formed symmetric synapses on dendritic profiles in this region, consistent with innervation of granule cells. Patterned illumination of ChR2-labeled fibers in s. lacunosum-moleculare of CA1 and the dentate molecular layer elicited GABAergic inhibitory responses in dentate granule cells in pilocarpine-treated mice but not in controls. Similar optical stimulation in the dentate hilus evoked no significant responses in granule cells of either group of mice. These findings indicate that under pathological conditions, SOM/GABAergic neurons can undergo substantial axonal reorganization beyond their normal territory and establish aberrant synaptic connections. Such reorganized circuitry could contribute to functional deficits in inhibition in epilepsy, despite the presence of numerous GABAergic terminals in the region.
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PMID:A reorganized GABAergic circuit in a model of epilepsy: evidence from optogenetic labeling and stimulation of somatostatin interneurons. 2400 92

Somatostatin, a natural inhibitor of growth hormone (GH), and its analogs have been used in clinical settings for the treatment of acromegaly, gigantism, thyrotropinoma, and other carcinoid syndromes. However, natural somatostatin is limited for clinical usage because of its short half-life in vivo. Albumin fusion technology was used to construct long-acting fusion proteins and Pichia pastoris was used as an expression system. Three fusion proteins (SS28)(2)-HSA, (SS28)(3)-HSA, and HSA-(SS28)(2), were constructed with different fusion copies of somatostatin-28 and fusion orientations. The expression level of (SS28)(3)-HSA was much lower than (SS28)(2)-HSA and HSA-(SS28)(2) due to the additional fusion of the somatostatin-28 molecule. MALDI-TOF mass spectrometry revealed that severe degradation occurred in the fermentation process. Similar to the standard, somatostatin-14, all three fusion proteins were able to inhibit GH secretion in blood, with (SS28)(2)-HSA being the most effective one. A pharmacokinetics study showed that (SS28)(2)-HSA had a prolonged half-life of 2 h. These results showed that increasing the number of small protein copies fused to HSA may not be a suitable method for improving protein bioactivity.
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PMID:The effect of albumin fusion structure on the production and bioactivity of the somatostatin-28 fusion protein in Pichia pastoris. 2475 60


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