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U Eder

Publications and source records attributed to U Eder.

18 recordsLinked to original sources
PubMed2000

Levels and molecular properties of secretoneurin-immunoreactivity in the serum and urine of control and neuroendocrine tumor patients.

We have determined the levels of secretoneurin (SN), a novel 33-amino acid neuropeptide belonging to the class of chromogranins, in the serum and urine of healthy subjects and patients suffering from various tumors. SN serum levels averaged 22.1+/-1.1 fmol/mL. They were 5-fold higher in younger children and then declined continuously. SN levels were positively correlated with serum creatinine, suggesting an influence of renal function on the clearance of SN from the serum. In the urine 80.0 fmol/mL SN was present. In patients with endocrine tumors like gut carcinoids, endocrine pancreatic tumors, oat cell lung carcinomas, and pheochromocytomas, SN serum levels were elevated up to 45-fold. Patients suffering from neuroblastomas, insulinomas, pituitary adenomas including acromegaly, and solid nonendocrine tumors had concentrations in the normal range. In human serum, SN-immunoreactivity was confined to the free peptide SN; neither larger intermediate-sized forms nor the precursor secretogranin II were detected. An efficient removal of the small molecule SN from the serum by the kidney explains why SN serum levels are lower when compared to chromogranin A, which is present as large molecule in serum.

Adolescent↗
PubMed1998

Levels and molecular forms of chromogranins in human childhood neuroblastomas and ganglioneuromas.

The chromogranins are a class of acidic proteins found in large secretory granules of neuroendocrine tissues and tumors derived from them. We measured the relative amounts and characterized the molecular forms of two members of this family, i.e. chromogranin A and secretogranin II, in 14 neuroblastomas and five ganglioneuromas. In all the tumors investigated significant amounts of chromogranin A and secretogranin II were found. Neuroblastomas contained two times and ganglioneuromas 45 times more secretogranin II compared to chromogranin A. Both proteins were processed in these tumors to a great extent to smaller peptides, only limited amounts of intact chromogranin A or secretogranin II were present. In general, proteolytic processing of secretogranin II to the small neuropeptide secretoneurin was more complete than that of chromogranin A to the peptide GE-25. Proteolytic processing of both chromogranins as well as the total amounts of these proteins were unrelated to tumor staging.

Adrenal Gland Neoplasms↗
PubMed1998

Levels and proteolytic processing of chromogranin A and B and secretogranin II in cerebrospinal fluid in neurological diseases.

Human cerebrospinal fluid (CSF) contains chromogranin A and B and secretogranin II which represent peptides secreted from neuronal large dense core vesicles. Within these vesicles these precursor peptides are at least partly processed to smaller peptides. We analysed the CSF levels of chromogranins/secretogranin by radioimmunoassay using specific antisera. The degree of their processing was characterized by molecular sieve column chromatography followed by radioimmunoassay. As previously shown secretogranin II is fully processed to smaller peptides including the peptide secretoneurin, whereas processing of chromogranin A was more limited. For chromogranin B we found in this study a high degree of processing comparable to that of secretogranin II. An analysis of CSF from patients with multiple sclerosis, essential tremor, Alzheimer and Parkinson disease, did not reveal any differences in proteolytic processing of chromogranins/secretogranin when compared to control CSF. We conclude that in the four diseases investigated there is no change in the proteolytic processing of the chromogranins/secretogranin within the large dense core vesicles. The absolute levels of chromogranins/secretogranin varied in CSF collected in different hospitals, however their relative ratios were remarkable constant. We suggest to use this ratio as a parameter to standardise CSF levels of other peptides, e.g. neuropeptides. In Parkinson patients the chromogranin A/secretogranin II ratio was significantly increased whereas in Alzheimer patients and those with essential tremor and multiple sclerosis no change of the ratios was observed. Apparently there are only limited changes in the biosynthesis, processing, secretion and CSF clearance of these peptides in pathological conditions.

Adult↗
PubMed1998

Presence of chromogranins and regulation of their synthesis and processing in a neuroendocrine prostate tumor cell line.

BACKGROUND: Small-cell carcinoma and carcinoid tumors of the prostate display a neuroendocrine phenotype. To some extent, adenocarcinomas of the prostate also express neuroendocrine properties. Prostatic neuroendocrine tumors do not respond to androgen ablation therapy. The regulation of synthesis of chromogranins and their processing into neuropeptides have not yet been studied in neuroendocrine cells of the prostate. We used CRL-5813 cells which were derived from a metastasis from small-cell prostate cancer for studies on steroid receptor expression and chromogranin processing. METHODS: The expression of steroid receptor mRNA in CRL-5813 cells was examined by polymerase chain reaction. The synthesis and secretion of chromogranin- and secretogranin II-derived peptides were investigated by radioimmunoassays and high-performance liquid chromatography in untreated cells and in cells treated with the protein kinase A activator forskolin or basic fibroblast growth factor (bFGF). RESULTS: cDNA fragments for alpha-estrogen receptor and androgen receptor but not for beta-estrogen receptor, progesterone receptor, and glucocorticoid receptor were amplified from CRL-5813 cells. These cells were found to contain typical markers of large dense-core vesicles, i.e., chromogranins A and B and secretogranin II. Forskolin significantly stimulated the synthesis and secretion of the chromogranin B-derived peptide PE-11 and the secretogranin II-derived secretoneurin. bFGF significantly induced PE-11 protein levels in cell extracts. CONCLUSIONS. Our results demonstrate the expression of typical large dense-core vesicle proteins, i.e., chromogranins, in a small-cell prostate cancer cell line and their upregulation by a protein kinase A activator and, in part, by bFGF.

Cell Line↗
PubMed1997

The presence of secretoneurin in human synovium and synovial fluid.

Secretoneurin is a neuropeptide formed from the proprotein secretogranin II. It is found in afferent nerve fibres and has chemotactic activity for monocytes, neutrophils and fibroblasts. We investigated the presence of secretoneurin in synovial fluid and synovium from patients with osteoarthritis and rheumatoid arthritis. The secretoneurin immunoreactive material found in synovial fluid was identified by high performance liquid chromatography as the free peptide secretoneurin. Its level in hip joints was 15.6, in knee joints of osteoarthritis patients 17.3 and in rheumatoid patients significantly lower (8.6 fmol/ml). Immunocytochemistry provided evidence for the presence of sub-intimal secretoneurin-immunoreactive nerve fibres in knee synovium in osteoarthritic patients. In rheumatoid synovium, only very few immunoreactive fibres were found these being mostly localised in deep stroma. The results show that secretoneurin is present in osteoarthritic joint and suggest that secretoneurin levels are down-regulated in rheumatoid joint. Therefore, secretoneurin may participate in acute or mild phases of inflammation but is unlikely to have a major role when more severe inflammation is present such as that seen in rheumatoid joint.

Antibody Specificity↗
PubMed1997

Secretoneurin: a new neuropeptide in the rodent pineal gland.

The pineal gland of mammals is richly innervated by nerve fibres containing various peptides of central or sympathetic origin. In this study, we have investigated the presence, regulation and effect of secretoneurin (SN), a 33-amino-acid peptide discovered recently in the central and sympathetic nervous systems. The rat pineal gland contains about 34 fmol SN/pineal, although only 20% of the secretoneurin immunoreactivity (SN-IR) is the free peptide. SN-IR is localised in only a few nerve fibres found in the parenchyma of the gland and along the pineal stalk. In the rat pineal, SN-IR shows no midday/midnight differences but is significantly decreased (55%-65%) after superior cervical ganglionectomy or exposure to constant light. These observations suggest that, in the rat pineal, SN-IR originates partly from central areas and partly from the superior cervical ganglia. The pineal of the Syrian hamster contains much more SN-IR: 120 fmol SN-IR/pineal (about 20% being the free peptide). SN-IR is found both in nerve fibres and pineal cells. Some of the fibres run along the pineal stalk, indicating that they are of central origin, although a sympathetic origin cannot be ruled out. Pineal SN-IR is below detectable levels in the Siberian hamster. In cultured rat pinealocytes, SN significantly inhibits serotonin release and, to a lower extent, melatonin release.

Animals↗
PubMed1997

Obstructive ileus of large bowel is associated with low tissue levels of neuropeptides in prestenotic bowel segment.

The neuropeptides substance P, vasoactive intestinal polypeptide, and the recently discovered peptide secretoneurin are neurotransmitters of the intrinsic nervous system of the gut and effect gut motility. The aim of this study was to investigate whether these neuropeptides are involved in the pathophysiology of large bowel ileus. Five patients underwent colonic resections for obstructive cancer of the colon. Full-thickness specimens of the resected colon were taken 10 cm proximal and 10 cm distal to the site of tumor obstruction. Substance P-, vasoactive intestinal polypeptide-, and secretoneurin-like immunoreactivities were measured in the specimens by radioimmunoassay. In addition immunocytochemistry was performed. Tissue levels of substance P, vasoactive intestinal polypeptide, and secretoneurin were lower in the prestenotic than in the poststenotic bowel segment. In accordance, immunocytochemistry revealed a denser staining of ganglion cells and fibers for all three neuropeptides in the poststenotic bowel. The decreased tissue levels of substance P, vasoactive intestinal polypeptide, and secretoneurin in the prestenotic bowel segment may contribute to the final decompensation of obstructive ileus.

Aged↗
PubMed1996

Localization and axotomy-induced regulation of the peptide secretoneurin in the rat superior cervical ganglion.

This study demonstrates the localization and regulation of a novel neuropeptide of 33 amino acids, secretoneurin (SN), in the rat superior cervical ganglion. Gel filtration chromatography of ganglion proteins followed by a specific radioimmunoassay revealed that SN is the predominant cleavage product of secretogranin II, a member of the chromogranin/secretogranin protein family, in adult ganglia. SN was detected within the majority of nerve endings surrounding postganglionic neurons that were identified by the presence of synaptophysin and, in part, colocalized leu-encephalin. Applying immuno-electronmicroscopy, SN was localized to large dense core vesicles of neuronal and small intensely fluorescent (SIF) cells. In situ hybridization revealed the presence of secretogranin II mRNA in postganglionic neurons and, to a lesser extent, in SIF cells. One week after transection of the postganglionic branches SN levels were not significantly altered; however, a decrease of secretogranin II mRNA was observed in postganglionic neurons but not in SIF cells. After decentralization of the ganglion, SN-immunoreactive nerve terminals disappeared and intraganglionic SN levels were reduced by 70%, indicating the preganglionic origin of SN-positive nerve fibres and varicosities. Secretogranin II mRNA was slightly reduced under this condition. Combined axotomy and decentralization further diminished intraganglionic secretogranin II mRNA, although peptide levels increased significantly above control values under these conditions. Double-labelling immunofluorescence with antibodies against the somatodendritic marker microtubule-associated protein 2 (MAP2) revealed that the increase in SN immunoreactivity was due to an accumulation of SN in axonal processes of postganglionic neurons. SN immunoreactivity was also detected in dissociated neonatal superior cervical ganglion cultures and increased significantly upon treatment with nerve growth factor, the survival and differentiation factor of sympathetic neurons during perinatal development. Co-culture with non-neuronal cells or addition of leukaemia inhibitory factor, a cytokine known to stimulate synthesis of various peptides after nerve transection, did not influence SN immunoreactivity. Therefore, since no fixed relationship between SN and any of the known neuropeptides or neurotransmitters expressed in sympathetic neurons was observed, the expression of this novel peptide appears to be independently regulated.

Animals↗
PubMed1995

Neural and mesenchymal differentiations in Ewing's sarcoma cell lines. Morphological, immunophenotypic, molecular biological and cytogenetic evidence.

Three established Ewing's sarcoma (ES) cell lines (TC106, 6647, A4573), grown both in vitro and as xenograft tumors, were analyzed. In all 3 lines and tumors, the ES characteristic reciprocal translocation (11;22), as well as the presence of the ES-associated p30/32MIC2 antigen, were documented. However, these cell lines showed discrepancies in their neural and mesenchymal differentiation. The TC106 line was characterized by expression of the neuroendocrine marker secretogranin II (SgII) which was detectable by Northern blot and by radioimmunological detection (RIA) in the culture medium of secretoneurin, a proteolytic product of SgII. In contrast, TC106 cells were immunohistochemically and radioimmunologically secretoneurin-negative. Rapid cellular secretion of the peptide is probably the explanation of such a discrepancy. The 6647 and A4573 cell lines were SgII/secretoneurin-negative and the former presented morphological and immunocytochemical evidence of mesenchymal differentiation. In fact, the 6647 xenograft tumor showed osteosarcomatous-type morphological features and the neoplastic cells were immunocytochemically positive for osteonectin and osteocalcin antigens. Expression of the CgA gene, which is typical of neuroblastomas, was absent in the Ewing's sarcoma cell lines investigated. Our findings provide experimental evidence that Ewing's sarcoma is a heterogeneous tumor which may show either neuroectodermal or mesenchymal differentiation. SgII/secretoneurin analysis by hybridization and RIA procedures is a reliable approach to the identification of ES with neuroendocrine differentiation.

Animals↗
PubMed1995

Processing of secretogranin II by prohormone convertases: importance of PC1 in generation of secretoneurin.

Secretoneurin is a recently characterized neuropeptide present in the primary amino acid sequence of secretogranin II. We investigated the proteolytic processing of secretogranin II by prohormone convertases in vivo in a cellular system using the vaccinia virus system. Both PC1 and PC2 can cleave the secretogranin II precursor at sites of pairs of basic amino acids to yield intermediate-sized fragments. Other convertases like PACE4, PC5 and furin were not active. For the formation of the free neuropeptide secretoneurin a different pattern was found. Only PC1 but none of the other convertases tested including PC2 were capable of generating secretoneurin. Our results demonstrate that the prohormone convertases PC1 and PC2 are involved in proteolytic processing of secretogranin II. The neuropeptide secretoneurin can only be generated by PC1 suggesting tissue-specific processing of secretogranin II in neurons expressing different subsets of the prohormone convertases.

Adrenal Medulla↗
PubMed1995

Secretoneurin: a new peptide in the human enteric nervous system.

Secretoneurin is a functional neuropeptide derived from secretogranin II (chromogranin C). This proprotein is processed to varying degrees in neuroendocrine tissues. In the present study we established by gel filtration high performance liquid chromatography that in human intestinal wall and mucosa an antiserum against secretoneurin detects as the major immunoreactive moiety the free peptide secretoneurin. In the mucosa some larger immunoreactive peptides were also present, however, a significant amount of the intact proprotein secretogranin II could not be detected. By immunohistochemistry we studied the distribution of secretoneurin within the gut. Antibodies to protein gene product 9.5 and chromogranin A were used to identify all neurons and endocrine cells, respectively, whilst those to the peptides substance P, CGRP and somatostatin were used for the further characterization of individual secretoneurin-positive structures. Secretoneurin immunoreactivity was found in nerve fibres in all layers of the gut wall. In both myenteric and submucous plexuses, nerve fibres and the majority of ganglion cells were secretoneurin-immunoreactive. In the mucosa, some secretoneurin-positive nerve processes ran parallel to the basal membrane of epithelial cells, occasionally invading the epithelial layer. Secretoneurin immunoreactivity was found in endocrine cells, mostly D cells, in the following regions in descending order of density: stomach/duodenum; rectum; colon; ileum. Thus, secretoneurin is a new major peptide within the human enteric neuroendocrine system. Its presence in abundant myenteric ganglion cells may imply a role in the modulation of gastrointestinal motility. The chemotactic properties of secretoneurin and its possible localization in sensory fibres suggest that this peptide may be involved in the genesis of intestinal inflammation.

Adult↗