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)

We have identified a series of mutations in the signal peptide of yeast prepro-alpha-factor which specifically attenuate translocation across the endoplasmic reticulum membrane in vivo. In prepro-alpha-factor-somatostatin hybrids, transposition of the amino-terminal tripeptide from wild-type NH2-Met-Arg-Phe to NH2-Met-Phe-Lys or NH2-Met-Phe-Arg causes a 45-75% reduction in the efficiency of membrane translocation. This is evidenced by the intracellular accumulation of unglycosylated, signal-containing precursors which are membrane-associated and are exposed to the cytosol. Surprisingly, abolition of the single positive charge by replacing arginine with phenylalanine has little effect on translocation into the endoplasmic reticulum. We conclude that the presence of an amino-terminal positive charge is not necessary for efficient targeting or translocation; however, misplacement by one position markedly disrupts translocation without affecting targeting. These mutations thus define an early stage of membrane interaction that is sensitive to local charge effects. Furthermore, our data suggest that post-translational translocation, signal cleavage, and core glycosylation of these polypeptides may occur to a significant extent in vivo.
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PMID:Misplacement of the amino-terminal positive charge in the prepro-alpha-factor signal peptide disrupts membrane translocation in vivo. 256 73

We have investigated the role of the somatostatin propeptide in mediating intracellular transport and sorting to the regulated secretory pathway. Using a retroviral expression vector, two fusion proteins were expressed in rat pituitary (GH3) cells: a control protein consisting of the beta-lactamase signal peptide fused to chimpanzee alpha-globin (142 amino acids); and a chimera of the somatostatin signal peptide and proregion (82 amino acids) fused to alpha-globin. Control globin was translocated into the endoplasmic reticulum as determined by accurate cleavage of its signal peptide; however, alpha-globin was not secreted but was rapidly and quantitatively degraded intracellularly with a t 1/2 of 4-5 min. Globin degradation was insensitive to chloroquine, a drug which inhibits lysosomal proteases, but was inhibited at 16 degrees C suggesting proteolysis occurred during transport to the cis-Golgi apparatus. In contrast to the control globin, approximately 30% of the somatostatin propeptide-globin fusion protein was transported to the distal elements of the Golgi apparatus where it was endoproteolytically processed. Processing of the chimera occurred in an acidic intracellular compartment since cleavage was inhibited by 25 microM chloroquine. 60% of the transported chimera was cleaved at the Arg-Lys processing site in native prosomatostatin yielding "mature" alpha-globin. Most significantly, approximately 50% of processed alpha-globin was sorted to the regulated pathway and secreted in response to 8-Br-cAMP. We conclude that the somatostatin propeptide mediated transport of alpha-globin from the endoplasmic reticulum to the trans-Golgi network by protecting molecules from degradation and in addition, facilitated packaging of alpha-globin into vesicles whose secretion was stimulated by cAMP.
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PMID:The propeptide of preprosomatostatin mediates intracellular transport and secretion of alpha-globin from mammalian cells. 256 5

Cells that produce somatostatin are widely distributed throughout the digestive tube. They are found in the stomach, small bowel, large bowel and pancreas. The authors used 54 Wistar rats, with an approximate weight of 300 gr, to evaluate the possible variations of the D cell population in isolated and functional intestinal segments, using jejuno-ileal bypass as a model. Rats were divided into three groups, a control group and two groups in which simple derivation techniques were performed following the techniques of Payne and DeWind, and Scott. Rats were sacrificed after 7, 30 and 90 days in subgroups of six animals. Macroscopic, microscopic and ultrastructural studies were carried out. Cells were specifically stained using immunocytochemical techniques (PAP). The corresponding values of the mucous areas were obtained using a computerized image analyzer (Quantimet 800) and then the number of D cells per mm2 mucosa was calculated. The results show a decrease in the number of D cells per mm2 of mucosa in the functional intestinal segments and degranulation of these cells, coinciding with the existence of large areas of rough endoplasmic reticulum (sign of cellular hyperactivity).
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PMID:[Changes induced by simple jejuno-ileal by-pass models in the distribution of D-cells producing intestinal somatostatin. Experimental study]. 257 88

Four endocrine cell types were identified using peroxidase-antiperoxidase (PAP) technique and ultrastructurally characterized in the pancreas of Mauremys caspica in both winter and summer. In winter, insulin-immunoreactive cells were more abundant and the cell groups larger in the splenic than in the duodenal region, whereas in summer, medium or small cell groups were evenly distributed. Glucagon- and somatostatin-immunoreactive cells were found throughout the gland; they were more numerous in the splenic than in the duodenal region. Polypeptide pancreatic (PP)-immunoreactive cells were found only in the duodenal region. Somatostatin-immunoreactive cells were mainly isolated in winter and grouped in summer. Glucagon- and PP-immunoreactive cells had a similar arrangement in both seasons. Somatostatin- and PP-containing cells showed cytoplasmic processes and could be found next to the pancreatic ducts; the latter were also observed near insulin-immunoreactive cells. Some large secretory granules and numerous, isolated and long rough endoplasmic reticulum (RER) cisternae were seen in winter B cells; in summer B cells numerous lysosomes and few, dilated RER cisternae were found. Summer A cells showed well-developed, dilated RER cisternae and numerous vacuoles; secretory granules were more numerous in winter A cells. In winter B cells and summer A cells some nuclear filamentous inclusions were observed. Few RER cisternae were observed in winter D cells and many in summer D cells; secretory granules were found, the shape and electron density of which differed with the season. PP cells were characterized by their small secretory granules, which were less numerous in winter than in summer, being clustered at the cell pole or dispersed in the cytoplasm, respectively; in winter, the well-developed RER cisternae were dilated and irregularly distributed.
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PMID:Comparative study on the endocrine cells in the pancreas of Mauremys caspica (chelonia) in summer and winter. 267 1

The biologically active forms of somatostatin, somatostatin-14 (SS-14) and somatostatin-28 (SS-28) arise by post-translational cleavage of prosomatostatin. Prosomatostatin in turn is derived from a larger precursor, preprosomatostatin. We have previously reported the structure of a complementary DNA molecule encoding rat preprosomatostatin. The nucleotide sequence of this cDNA indicated that SS-14 and SS-28 are located at the carboxy-terminus of a 116 amino acid precursor. At the amino-terminus of the precursor is a hydrophobic region characteristic of a leader or pre-sequence. Sequential Edman degradations of cell-free translation products synthesized in the presence of microsomal membranes indicate that preprosomatostatin is cleaved within the endoplasmic reticulum to form prosomatostatin, a precursor of 92 amino acids. To begin to elucidate the factors which regulate the expression of the rat somatostatin gene, we have determined the sequence of the gene isolated from recombinant bacteriophage libraries. The gene spans 1.2 kilobases in length and is interrupted within the coding sequence of prosomatostatin by a single intron of 630 bases. A variant of the Goldberg-Hogness promotor, TTTAAA, is located 31 bases upstream from the transcriptional start point. A repetitive sequence was identified in the 5' region of the gene within 650 bases of the promoter. The nucleotide sequence of this region reveals an alternating GT sequence 42 bases in length characteristic of DNA with Z-forming potential. Such sequences are thought to influence the expression of other eukaryotic genes.
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PMID:Biosynthesis of rat preprosomatostatin. 286 39

Immunocytochemical and ultrastructural methods have shown four cell types in the endocrine pancreas of the turtle Pseudemys scripta elegans: insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-immunoreactive cells. Each endocrine cell type was distributed differently in the duodenal or splenic regions of the turtle pancreas. Round or fusiform insulin- and glucagon-containing cells could be seen as single scattered cells which were more numerous in the duodenal regions, and the cell groups becoming progressively smaller from splenic to duodenal region. Round or fusiform somatostatin cells with thick processes and spindly pancreatic polypeptide cells with long protrusions were less numerous the nearer they were to the splenic regions; they were isolated in the duodenal zone. Insulin cells were surrounded by somatostatin cells and an outer layer of glucagon cells around the cell groups could be seen. Insulin cells were characterized by their round secretory granules which contained a polygonal, irregular or rod-shaped dense core. They also contained numerous clustered mitochondria, large multivesicular bodies, and cilium. Glucagon cells, joined by desmosomes to adjacent ones, had numerous filamentous mitochondria with longitudinal cristae and round electron-dense secretory granules with closely applied membrane. Somatostatin cells contained two kinds of secretory granules, some of which showed an electron-dense core, while others had moderately electron-dense floccular material. PP cells were characterized by round secretory granules, smaller than those of other cell types, and a large euchromatinic nucleus. Lysosomes, microtubules, bundles of microfilaments, a well-developed Golgi apparatus, and scarce rough endoplasmic reticulum were present in the cytoplasm of all these endocrine cell types.
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PMID:An immunocytochemical and ultrastructural study of the endocrine pancreas of Pseudemys scripta elegans (Chelonia). 286 92

The distribution of somatostatin-immunoreactive cell bodies and axons throughout the human isocortex and subjacent white matter was examined. Vibratome sections of cortical tissue (30-40 micrometers thick) obtained at surgery were treated to reveal the antigen by the unlabelled antibody enzyme method. Two types of somatostatin-immunoreactive axons were present: short, coiled axons and extended ones that follow a straight course in various directions. Somatostatin immunoreactive nerve cell bodies were encountered in layers II-VI and in the subjacent white matter. The majority of labelled cells were found in the white matter and layer VI, and then in layers II and III. The immunoreactive perikarya were fusiform, triangular or multipolar in shape and did not show preferential orientation of their long axis. Frequently, the fusiform neurons in layer VI and in the white matter were aligned parallel to radiate bundles of myelinated fibres. The immunoreactive neurons gave rise to a few thick dendrites. Often thin axon-like processes could also be recognized, originating either from the cell body or from a thicker dendrite. After destaining of the chromogen and counterstaining with aldehydefuchsin and gallocyanin chromealum, the formerly immunoreactive neurons displayed a light and eccentrically located nucleus. The soma contained only a sparse amount of basophilic substance and was nearly devoid of lipofuscin granules. In electron micrographs, the cisterns of the rough endoplasmic reticulum (RER) were localized near the periphery of the soma. Immunoreactivity occurred along membranes of the RER cistern, outer mitochondrial membrane, and in particles 120-150 micrometers in diameter. Rounded areas (up to a diameter of 1 micrometer) lacked immunoreactivity. Furthermore, there were a few tiny lysosomes.
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PMID:Somatostatin-like immunoreactivity in non-pyramidal neurons of the human isocortex. 286 17

Tris(hydroxymethyl)aminomethane (Tris) has been shown to inhibit selectively the Golgi apparatus and Golgi-endoplasmic reticulum-lysosomal system (GERL system) of several kinds of cells including pancreatic B cells. This study was designed to assess the effect of Tris on insulin, glucagon and somatostatin release and insulin synthesis in pancreatic B cells by using isolated rat pancreatic islets. Tris suppressed glucose-induced insulin release, whereas it did not affect the glucagon and somatostatin release. Furthermore, the incorporation of [3H]leucine into the insulin fraction was suppressed by 10 mM Tris, but the sum of the radioactivity of both proinsulin and insulin fraction were not influenced. The present study suggests that the Golgi apparatus and GERL system may play a role in insulin secretion and biosynthesis in pancreatic B cells.
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PMID:Effects of tris(hydroxymethyl)aminomethane on biosynthesis and release of insulin in the pancreatic Langerhans islets. 287 7

The distribution and fine structure of somatostatin-like immunoreactive neurons in rat hippocampus and gyrus dentatus were investigated by light and electron microscopic immunocytochemistry. Somatostatin-like immunoreactive neuronal perikarya and fibers could be visualized by using modified PAP immunocytochemistry. Immunoreactive neurons were selectively localized in the stratum orience of the hippocampus and hilar region of the gyrus dentatus, however, immunoreactive neurons were also sparsely observed throughout hippocampal formation. Somatostatin-like immunoreactive varicosities were abundantly distributed in the stratum pyramidale and some of them were considered to terminate on the pyramidal cells. Somatostatin-like immunoreactive neurons in the hippocampal formation generally contained many mitochondria, well-developed rough surfaced endoplasmic reticulum (rER), polysomes and some dense granules. Immunoreactivity was observed especially in the dense granules and membrane of rER. Pre- and post-synaptic elements of somatostatin-like immunoreactive neurons were detected throughout the hippocampal formation.
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PMID:Light and electron microscopic study of somatostatin-like immunoreactive neurons in rat hippocampus. 288 97

The present study reports the effects of SMS 201-995, a long-acting somatostatin analogue, on blood GH levels, glucose tolerance and tumour morphology in a 36-year-old, previously untreated acromegalic woman. Treatment (50 micrograms s.c., 8-hourly) resulted in marked suppression of GH concentration and an improvement in glucose tolerance. After 10 d of treatment, the tumour was removed by transsphenoidal surgery and studied by histology, immunohistochemistry, transmission electron microscopy and morphometry. Histologically, the tumour was an acidophilic adenoma which contained immunoreactive GH in many adenoma cells. By electron microscopy, the tumour was composed of densely granulated somatotrophs containing numerous large secretory granules and many lysosomes showing crinophagy. No cell necrosis or vascular impairment were evident. Using morphometry, the tumour was compared with 10 densely granulated somatotroph adenomas, removed from acromegalic patients not treated with somatostatin. The nuclear and cytoplasmic areas of the adenoma subjected to SMS 201-995 treatment were smaller, and the lysosomes occupied more of the cytoplasmic volume than those of controls. The nuclear/cytoplasmic ratio, cytoplasmic volume densities of endoplasmic reticulum, Golgi apparatus, mitochondria, secretory granules and secretory granule diameters were within the range of control adenomas. In vitro, treated adenoma cells secreted GH and retained responsiveness to both GRH stimulation and somatostatin suppression. The morphologic findings after SMS 201-995 treatment, are consistent with suppression of GH release. There is no evidence that somatostatin has any direct cytotoxic or vasotoxic effects. It appears that SMS 201-995 represents a potent and promising drug in the medical treatment of acromegaly, however, more work is needed to elucidate the mechanism of somatostatin suppression and to provide evidence for adenoma shrinkage.
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PMID:Effect of SMS 201-995, a long-acting somatostatin analogue, on the secretion and morphology of a pituitary growth hormone cell adenoma. 288 49


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