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)

The immunocytochemical distribution and messenger RNA expression of the prohormone convertases PC1 and PC2 involved in the posttranslational processing of precursor proteins were analyzed in mouse and rat pancreatic islets. Immunocytochemical colocalization studies demonstrated a close association of insulin with both PC1 and PC2 in the adult mouse and rat pancreas. The coexpression of insulin with the prohormone convertases was further examined in rat pancreatic tumors induced by streptozotocin-nicotinamide treatment. These insulin-synthesizing tumors expressed PC1 and PC2, whereas insulin-silent adenomas did not. Colocalization studies demonstrated that only PC2, not PC1, colocalizes with glucagon, pancreatic polypeptide, and somatostatin. The highest levels of PC2-like immunoreactivity were observed in the glucagon-containing alpha-cells. Ontogeny studies carried out by in situ hybridization in mice showed the first detectable expression of the prohormone convertases in the pancreatic primordium at midgestation, starting for PC1 on embryonic day 11 and for PC2 on embryonic day 10. Enzyme expression was further confirmed by immunocytochemistry, which detected the presence of immunoreactive PC1- and PC2-like proteins on embryonic days 14 and 17, respectively. Taken together, our data suggest that both PC1 and PC2 play a role in proinsulin processing in vivo, whereas PC2 is a likely candidate convertase participating in the processing of proglucagon, propancreatic polypeptide, and prosomatostatin in pancreatic islets.
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PMID:Developmental expression of the prohormone convertases PC1 and PC2 in mouse pancreatic islets. 792 29

Changes in transcription factor and neuropeptide gene expression are likely to be involved in the cascade of genetic and molecular events leading to permanent changes in neuronal activity associated with kindling and epilepsy. Both acute-transient and delayed-sustained changes in transcription factor or immediate early gene (IEG) activity have previously been reported in response to different stimuli. In the present study in situ hybridization was used to investigate the possible time course (30 min-8 week) of IEG and neuropeptide mRNA induction in forebrain in a kindling model of epilepsy. Kindling was produced by daily unilateral stimulation of the amygdala. IEG mRNAs were detected using [35S]-labelled oligonucleotide probes specific for c-fos, c-jun, NGFI-A (PC1) and PC3 transcripts. Possible changes in the level of mRNAs encoding the neuropeptides somatostatin (SOM) and neuropeptide Y (NPY) were also studied. Stimulation-induced seizures produced dramatic bilateral increases in all IEG mRNAs in the dentate gyrus after 30 min to 1 h. Ipsilateral or bilateral increases in c-fos and PC3 mRNA were observed in the piriform cortex of individual animals at 30 min post-stimulation. While the distribution and apparent basal expression of the different IEGs varied (NGFI-A and c-jun > c-fos and PC3), the degree of induction in the dentate gyrus was similar for all IEGs studied (i.e. 200-300%). No long-term changes in IEG mRNA expression were detected beyond 2 h and up to 8 week after the last seizure. Increased levels of preproSOM and preproNPY mRNAs were consistently observed in hilar interneurons, but not in pyramidal or granule cells of the hippocampus, after 1-2 h. These increases were not maintained at later times. The short-term effects on IEG and neuropeptide mRNAs observed suggest that these changes are consequence of seizure activity with the development of kindling. In contrast, no evidence was found of any substantial, long-lasting effects on these parameters associated with the established kindled state.
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PMID:Rapid and transient increases in cellular immediate early gene and neuropeptide mRNAs in cortical and limbic areas after amygdaloid kindling seizures in the rat. 898 7

A somatostatin deficit occurs in the cerebral cortex of Alzheimer's disease patients without a major loss in somatostatin-containing neurons. This deficit could be related to a reduction in the rate of proteolytic processing of peptide precursors. Since the two proprotein convertases (PC)1 and PC2 are responsible for the processing of neuropeptide precursors directed to the regulated secretory pathway, we examined whether they are involved first in the proteolytic processing of prosomatostatin in mouse and human brain and secondly in somatostatin defect associated with Alzheimer's disease. By size exclusion chromatography, the cleavage of prosomatostatin to somatostatin-14 is almost totally abolished in the cortex of PC2 null mice, while the proportions of prosomatostatin and somatostatin-28 are increased. By immunohistochemistry, PC1 and PC2 were localized in many neuronal elements in human frontal and temporal cortex. The convertases levels were quantified by Western blot, as well as the protein 7B2 which is required for the production of active PC2. No significant change in PC1 levels was observed in Alzheimer's disease. In contrast, a marked decrease in the ratio of the PC2 precursor to the total enzymatic pool was observed in the frontal cortex of Alzheimer patients. This decrease coincides with an increase in the binding protein 7B2. However, the content and enzymatic activity of the PC2 mature form were similar in Alzheimer patients and controls. Therefore, the cortical somatostatin defect is not due to convertase alteration occuring during Alzheimer's disease. Further studies will be needed to assess the mechanisms involved in somatostatin deficiency in Alzheimer's disease.
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PMID:The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease. 1461 8

Somatostatin (SST) is a biologically active peptide produced in neuroendocrine cells. In the present study, we provide evidence of pro-SST and SST receptor (SSTR1 and 2A) mRNA expression in ocular ciliary epithelium (CE). SST or SST-like immunoreactivity was detected by radioimmunoassay in tissue extract from ciliary processes and in aqueous humor. The distinct immunolabeling of CE with SST and proprotein convertases PC1 and PC2 antibodies suggested a tissue and cell-specific processing of pro-SST. SST (10(-8) to 10(-4)M) added exogenously to the CE, elicited the following effects: (i) a dose-dependent attenuation of Na+/H+-exchanger (NHE) activity; (ii) up to a two-fold increase phosphorylation of p-Akt-Ser473 and of p-eNOS-Ser617, and (iii) lack of response on intracellular cyclic GMP production. LY294002, a PI3K-inhibitor, blocked SST-induced p-Akt-Ser473 and partially p-eNOS-Ser617, however, it did not reverse SST-induced NHE attenuation. Collectively, these results suggested involvement of SST in multiple intracellular signaling pathways in the CE.
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PMID:Somatostatin modulates PI3K-Akt, eNOS and NHE activity in the ciliary epithelium. 1676 85