Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin and octreotide share with vasoactive intestinal peptide the property of having an inhibitory effect on leukocyte functions. While there are studies reporting the inhibitory effect of the latter on respiratory burst in human monocytes, no such reports are available about similar inhibitory effects of the former. The aim of the present study was to investigate such effects of somatostatin and octreotide on human monocytes. Release of superoxide anion from monocytes was measured by superoxide dismutase-inhibitable reduction of cytochrome c in vitro. Somatostatin 1-14, somatostatin 1-28 and octreotide inhibited release of superoxide anion from stimulated monocytes. Formylpeptide-stimulated reduction of cytochrome c was inhibited by 1 mumol/l of octreotide and somatostatin 1-14 by about 50% and 35%, respectively. The effect was dose-dependent with half-maximal effective peptide concentrations at about 10 nmol/l. Somatostatin 1-28, which is the major form found in circulating plasma, also antagonized formylpeptide-stimulated respiratory burst activity; when directly compared to the effect of 1 mumol/l of somatostatin 1-14, somatostatin 1-28 was significantly more active (P less than 0.05). Our observations suggest that somatostatin-related peptides have a regulatory role in oxygen radical metabolism and a mediator role in the neuro-immune axis.
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PMID:Suppression of superoxide release from human monocytes by somatostatin-related peptides. 136 Jun 87

A peptide, eluted with cytochrome c, called 'big' somatostatin, is the only somatostatin-like immunoreactivity present in the peripheral plasma of the duck. The metabolic action of partially purified fractions of 'big' somatostatin was investigated on glucagon-stimulated lipolysis in chicken adipocytes. Significant inhibition of glycerol release (an index of lipolysis) induced by physiological concentrations of glucagon was observed with physiological concentrations of 'big' somatostatin; the percentage of inhibition was dose-dependent.
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PMID:The biological activity of duck 'big' somatostatin on chicken adipose tissue. 285 95

The conformation of some polypeptides and proteins in sodium dodecyl sulfate (NaDodSO4) solutions was studied by circular dichroism. The type and extent of induced structure depend on their helix- and beta-forming potential. Anionic side groups in segments of helix or beta form tend to destabilize the ordered structure unless they are protonated. beta-Endorphin has one Glu inside a predicted helical segment; its helicity in a NaDodSO4 solution is enhanced at pH below 4. alpha-Melanocyte-stimulating hormone having a Glu in a beta segment undergoes a pH-induced coil to beta transition in 1.25 mM NaDodSO4 (excess surfactant will disrupt the beta form). Reduced somatostatin assumes a beta form in 2 mM NaDodSO4 and a partial helix in 25 mM NaDodSO4, both of which are unchanged in acidic pH because it lacks -COOH groups. The unordered gastrin with five consecutive Glu's becomes helical in a NaDodSO4 solution at pH 4. Neurotensin with one Glu has no structure-forming potential and is unordered in both neutral and acidic NaDodSO4 solutions. This charge effect also manifests in segments of ordered structure for polypeptides and proteins such as glucagon, cytochrome c, parvalbumin, ribonuclease A, and lysozyme. The effect is especially predominant in tropomyosin that is rich in clusters of anionic side groups. Its more than 90% helicity is reduced to about one-half in a neutral NaDodSO4 solution, but most of it can be restored by lowering the pH to 2.4.
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PMID:Ordered conformation of polypeptides and proteins in acidic dodecyl sulfate solution. 611 37

A sensitive and specific radioimmunoassay without an extraction step was developed for somatostatin in duck plasma. Degradation of Tyr1-125I-labelled somatostatin-14 (S-14) averaged 2% for blood collected with EDTA and zymofren. Recovery of somatostatin-like immunoreactivity (SLI), added to the plasma, averaged 91% for S-14 and 86% for S-28. Chromatographic analysis of portal plasma on Sephadex G-25 showed three peaks: one peak coeluted with cytochrome c (mol. wt 12500) in the void volume and was called 'big' somatostatin; of the two smaller forms, one coeluted with synthetic S-28 and the other with synthetic S-14; these were immunologically and physicochemically indistinguishable from synthetic S-28 and S-14. In peripheral plasma only the large form of somatostatin, 'big' somatostatin, was found. The mean portal plasma concentration of SLI was 4.1 +/- 0.41 microgram/l (n = 11, range 2.8-5.1 micrograms/l). In peripheral plasma the SLI concentration was 1.05 +/- 0.45 microgram/l (n = 11, range 0.84-1.2 microgram/l). The metabolic clearance rate, distribution volume and calculated half-life values were 63.1 +/- 14 ml/kg per min, 40.9 +/- 8.9 ml/kg and 1.06 +/- 0.19 min for S-14 compared with 45.7 +/- 7 ml/kg per min, 14.8 +/- 2.5 ml/kg and 2.14 +/- 0.54 min for S-28. These results indicated that S-28 was cleared from plasma at a slower rate than S-14 in the duck. It was concluded that: (1) portal plasma SLI was four times higher than peripheral SLI; (2) SLI in portal plasma existed as 'big' somatostatin, S-28 and S-14, whereas in peripheral plasma it existed mainly as 'big' somatostatin; (3) in-vivo studies indicated that S-28 was metabolized less rapidly than S-14.
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PMID:Characterization of somatostatin in peripheral and portal plasma in the duck: in-vivo metabolism of somatostatin-28 and -14. 614 74

Activation of initiator and effector caspases, mitochondrial changes involving a reduction in its membrane potential and release of cytochrome c (cyt c) into the cytosol, are characteristic features of apoptosis. These changes are associated with cell acidification in some models of apoptosis. The hierarchical relationship between these events has, however, not been deciphered. We have shown that somatostatin (SST), acting via the Src homology 2 bearing tyrosine phosphatase SHP-1, exerts cytotoxic action in MCF-7 cells, and triggers cell acidification and apoptosis. We investigated the temporal sequence of apoptotic events linking caspase activation, acidification, and mitochondrial dysfunction in this system and report here that (i) SHP-1-mediated caspase-8 activation is required for SST-induced decrease in pH(i). (ii) Effector caspases are induced only when there is concomitant acidification. (iii) Decrease in pH(i) is necessary to induce reduction in mitochondrial membrane potential, cyt c release and caspase-9 activation and (iv) depletion of ATP ablates SST-induced cyt c release and caspase-9 activation, but not its ability to induce effector caspases and apoptosis. These data reveal that SHP-1-/caspase-8-mediated acidification occurs at a site other than the mitochondrion and that SST-induced apoptosis is not dependent on disruption of mitochondrial function and caspase-9 activation.
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PMID:Caspase-8-mediated intracellular acidification precedes mitochondrial dysfunction in somatostatin-induced apoptosis. 1073 62

Dynamic covalent chemistry is a versatile and powerful tool that integrates both stable chemical bonds and stimulus responsiveness into the construction of smart biotherapeutics. With minimalistic molecular design, a dynamic covalent protein assembly that incorporates selective targeting and intracellular release upon pH stimulus is presented. The construct comprises an active enzymatic protein core (cytochrome c) self-assembled with cancer cell targeting motifs (somatostatin) through boronic acid/salicylhydroxamate chemistry. The bioorthogonal assembly takes place rapidly under neutral aqueous conditions while the release of the protein is initiated under acidic conditions found within cellular vesicles during uptake. By demonstrating that these modular components act in synergy, we show the broad applicability of such chemical strategies to advance the frontier of modern nanomedicine.
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PMID:Dynamic Core-Shell Bioconjugates for Targeted Protein Delivery and Release. 3003 52