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Peptide Secretion (peptide + secretion)
Selected AbstractsMutagenesis studies in transgenic Xenopus intermediate pituitary cells reveal structural elements necessary for correct prion protein biosynthesisDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2007Jos W.G. van Rosmalen Abstract The cellular prion protein (PrPC) is generally accepted to be involved in the development of prion diseases, but its physiological role is still under debate. To obtain more insight into PrPC functioning, we here used stable Xenopus transgenesis in combination with the proopiomelanocortin (POMC) gene promoter to express mutated forms of Xenopus PrPC fused to the C-terminus of the green fluorescent protein (GFP) specifically in the neuroendocrine Xenopus intermediate pituitary melanotrope cells. Similar to GFP-PrPC, the newly synthesized GFP-PrPCK81A mutant protein was stepwise mono- and di-N-glycosylated to 48- and 51-kDa forms, respectively, and eventually complex glycosylated to yield a 55-kDa mature form. Unlike GFP-PrPC, the mature GFP-PrPCK81A mutant protein was not cleaved, demonstrating the endoproteolytic processing of Xenopus PrPC at lysine residue 81. Surprisingly, removal of the glycosylphosphatidylinositol (GPI) anchor signal sequence or insertion of an octarepeat still allowed N-linked glycosylation, but the GFP-PrPC,GPI and GFP-PrPCocta mutant proteins were not complex glycosylated and not cleaved, indicating that the GPI/octa mutants did not reach the mid-Golgi compartment of the secretory pathway. The transgene expression of the mutant proteins did not affect the ultrastructure of the melanotrope cells nor POMC biosynthesis and processing, or POMC-derived peptide secretion. Together, our findings reveal the evolutionary conservation of the site of metabolic cleavage and the importance of the presence of the GPI anchor and the absence of the octarepeat in Xenopus PrPC for its correct biosynthesis. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Information Processing in the Hypothalamus: Peptides and Analogue ComputationJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2006G. Leng Abstract ,Lovers and madmen have such seething brains,/Such shaping fantasies, that apprehend/More than cool reason ever comprehends'(A Midsummer Night's Dream, Act V Scene I) Peptides in the hypothalamus are not like conventional neurotransmitters; their release is not particularly associated with synapses, and their long half-lives mean that they can diffuse to distant targets. Peptides can act on their cells of origin to facilitate the development of patterned electrical activity, they can act on their neighbours to bind the collective activity of a neural population into a coherent signalling entity, and the co-ordinated population output can transmit waves of peptide secretion that act as a patterned hormonal analogue signal within the brain. At their distant targets, peptides can re-programme neural networks, by effects on gene expression, synaptogenesis, and by functionally rewiring connections by priming activity-dependent release. [source] Regulation of PSA secretion and survival signaling by calcium-independent phopholipase A2, in prostate cancer cellsTHE PROSTATE, Issue 12 2009Thomas M. Nicotera Abstract BACKGROUND Serum prostate specific antigen (PSA) levels in prostate cancer patients serve as a useful biomarker for diagnosing and monitoring prostate cancer. Recently, secreted PSA has been characterized as an autocrine survival factor through activation of Akt and induction of AR. In the normal prostate, PSA is secreted in the lumen of prostatic ducts to lyse proteins in the seminal coagulum. METHODS However, the mechanism for constitutive PSA secretion from benign prostate and its transport across the prostate-blood barrier into serum are unknown. Regulation of peptide secretion by iPLA2 -, has been reported in non-prostatic tissue and in prostate tissue iPLA2 -, is reported to be under androgen regulation. We investigated whether iPLA2 plays a role for in PSA secretion by comparing iPLA2 activity and expression in normal prostate epithelial RWPE-1 cells and in LNCaP prostate cancer cells. Expression of the two active iPLA2 -, mRNA splice variants, LH-iPLA2 and SH-iPLA2, were increased and the inhibitory ankyrin-iPLA2 isoform was markedly reduced in LNCaP cells as compared to normal prostate epithelial RWPE-1 cells. RESULTS These changes are consistent with a higher enzymatic activity in LNCaP cells. The iPLA2 -,-specific inhibitor BEL inhibited PSA secretion and induced apoptosis in LNCaP cells. iPLA2 knockdown using SiRNA inhibited PSA secretion, downregulated AR and induced apoptosis. Exogenous PSA suppressed BEL-induced apoptosis and neutralizing anti-PSA antibody blocked the survival effect of PSA. CONCLUSIONS These data indicate that iPLA2 -, participates in regulating PSA secretion and supports the concept that secreted PSA provides an autocrine survival function in LNCaP cells. Prostate 69:1270,1280, 2009. © 2009 Wiley-Liss, Inc. [source] The neuro-cardio-endocrine response to acute subarachnoid haemorrhageCLINICAL ENDOCRINOLOGY, Issue 5 2002Eric A. Espiner Summary objective Whereas cardiac hormones increase after subarachnoid haemorrhage (SAH), and may contribute to sodium wastage and hyponatraemia, there is controversy concerning the relative roles of atrial natriuretic peptide (ANP) vs. brain natriuretic peptide (BNP) and the factors initiating their secretion. Noting previous work linking stress hormone responses with cardiac injury after SAH, we have studied responses in stress hormones, markers of cardiac injury and the temporal changes in ANP and BNP and related them to changes in sodium status post ictus and during recovery from acute SAH. design, patients, measurements Eighteen patients with verified SAH of variable severity were studied in a single unit for a 14-day period post ictus under controlled conditions of sodium and fluid intake. All received a standardized protocol of daily dexamethasone and nimodipine throughout the study. Severity was graded using criteria of Hess and Hunt at admission. Stress hormones (AVP, catecholamines and admission plasma cortisol), markers of cardiac injury (ECG and daily plasma troponin T) and cardiac hormones (ANP and BNP) were measured daily and related to severity, plasma sodium and renin,aldosterone activity. Hormone levels (ANP, BNP and endothelin) in cerebrospinal fluid (CSF) were also measured in nine patients. results Intense neurohormonal activation (AVP, cortisol and catecholamines) at admission was associated with increased levels of both plasma ANP and BNP whereas levels in CSF were unaffected. In individual patients plasma levels of ANP and BNP were strongly correlated (P < 0·001). Cardiac events (abnormal ECG and/or elevated troponin) occurred in six of seven patients graded severe but neither stress hormones nor cardiac peptides differed significantly in patients with mild (n = 11) vs. severe (n = 7) SAH. During the course of a progressive fall in plasma sodium concentration (P = 0·001), there was a delayed activation of renin,aldosterone which was inversely correlated with declining levels of plasma ANP/BNP (P < 0·002). conclusions Excessive secretion of both ANP and BNP occurs in all patients after acute subarachnoid haemorrhage and is unrelated to severity, stress hormone activation or markers of cardiac injury. Inhibition of renin,aldosterone by cardiac hormones may impair renal sodium conservation and contribute to developing hyponatraemia. In the absence of evidence for activation of natriuretic peptides within the brain, the prompt and consistent increase in both ANP and BNP strongly supports the view that the heart is the source of increased natriuretic peptide secretion after acute subarachnoid haemorrhage. [source] | ||||||||||