Regulatory Peptides最新文献

{"title":"Evaluation of somatostatin receptor subtype expression in human neuroendocrine tumors using two sets of new monoclonal antibodies","authors":"Chiara Lambertini ,&nbsp;Patrizia Barzaghi-Rinaudo ,&nbsp;Lisa D'Amato ,&nbsp;Stefan Schulz ,&nbsp;Paolo Nuciforo ,&nbsp;Herbert A. Schmid","doi":"10.1016/j.regpep.2013.10.007","DOIUrl":"10.1016/j.regpep.2013.10.007","url":null,"abstract":"<div><h3>Introduction</h3><p><span><span>The expression and reliable detection of somatostatin receptor subtypes<span> (SSTR1–5) is a prerequisite for the successful use of somatostatin analogs in neuroendocrine tumors (NETs). Two sets of </span></span>monoclonal antibodies (mAbs) against human SSTR1, 2A, 3 and 5 have recently been developed by two independent laboratories using rabbit and mouse </span>hybridomas. Our aim was to evaluate the usefulness of both sets of mAbs for detection of SSTRs in NET samples as they are routinely collected in clinical practice.</p></div><div><h3>Methods</h3><p><span>Mouse and rabbit mAbs were characterized in SSTR1, 2A, 3 and 5-transfected HEK293 cells and human archival samples of pancreatic tissue and NET. Comparative analysis of mAbs was also conducted by immunostaining of a </span>tissue microarray composed of 75 cores of NET.</p></div><div><h3>Results</h3><p>Immunohistochemical analysis of HEK293 cells showed that both rabbit and mouse mAbs specifically detect their cognate receptor subtype, with mild cytoplasmic cross-reactivity observed for rabbit mAbs. Both sets of mAbs labeled normal pancreatic islets and showed similar patterns of immunoreactivity in NET controls. Direct comparison of mAb sets using a NET tissue microarray revealed strong correlation between rabbit and mouse mAbs against SSTR1 and 5, and moderate correlation for SSTR3. The rabbit mAb against SSTR2A showed higher affinity for its cognate receptor than the corresponding mouse mAb, resulting in a more reliable detection of this SSTR.</p></div><div><h3>Conclusions</h3><p>mAbs from both sets are reliable tools for the detection of SSTR1, 3 and 5, whereas the rabbit mAb against SSTR2A is recommended for use in routine clinical testing due to its superior binding affinity.</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"187 ","pages":"Pages 35-41"},"PeriodicalIF":0.0,"publicationDate":"2013-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.10.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31831334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat","authors":"Elin Sand ,&nbsp;Monika Bergvall ,&nbsp;Eva Ekblad ,&nbsp;Mauro D'Amato ,&nbsp;Bodil Ohlsson","doi":"10.1016/j.regpep.2013.09.002","DOIUrl":"10.1016/j.regpep.2013.09.002","url":null,"abstract":"<div><h3>Background</h3><p><span>Gonadotropin-releasing hormone (GnRH), luteinizing hormone<span> (LH), and follicle-stimulating hormone (FSH) regulate the reproductive axis. Their analogs have been found to influence gastrointestinal activity and enteric neuronal survival. The aims of the study were to investigate expression and cellular distribution of GnRH, LH, and FSH and their receptors in human and rat </span></span>gastrointestinal tract.</p></div><div><h3>Methods</h3><p><span><span>Bioinformatic analysis of publicly available microarray gene expression data and Real-Time PCR mRNA quantification were used to study </span>mRNA expression levels of hormones and receptors in human intestinal tissue. Full-thickness sections of human ileum and colon, and rat stomach, ileum, and colon, were used for </span>immunocytochemistry<span>. Antibodies against human neuronal protein HuC/D (HuC/D) were used as general neuronal marker. LH and FSH, and GnRH-, LH-, and FSH receptor immunoreactive (IR) neurons were evaluated.</span></p></div><div><h3>Results</h3><p><span>GnRH1 mRNA was detected in both small and large intestine, whereas GnRH2 was mainly expressed in </span>small intestine<span>. Approximately 20% of both submucous and myenteric neurons displayed LH receptor immunoreactivity in human ileum and colon. In rat, 4%–9% of all enteric neurons in fundus and ileum, and 13% of submucous neurons and 21% of myenteric neurons in colon were LH receptor-IR. Neither mRNA (man) nor the fully expressed proteins (man and rat) of LH and FSH, or GnRH and FSH receptors, could be detected.</span></p></div><div><h3>Conclusions</h3><p>GnRH1 and GnRH2 mRNA are expressed in human intestine. LH receptor-IR enteric neurons are found along the entire gastrointestinal tract in both man and rat.</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"187 ","pages":"Pages 24-28"},"PeriodicalIF":0.0,"publicationDate":"2013-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.09.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31788237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromedin B stimulates the hypothalamic–pituitary–gonadal axis in male rats","authors":"C.K. Boughton ,&nbsp;S.A. Patel ,&nbsp;E.L. Thompson ,&nbsp;M. Patterson ,&nbsp;A.E. Curtis ,&nbsp;A. Amin ,&nbsp;K. Chen ,&nbsp;M.A. Ghatei ,&nbsp;S.R. Bloom ,&nbsp;K.G. Murphy","doi":"10.1016/j.regpep.2013.10.002","DOIUrl":"10.1016/j.regpep.2013.10.002","url":null,"abstract":"<div><p><span><span><span>Neuromedin B (NMB) is a highly conserved bombesin-related peptide found in mammals. NMB mRNA is detected in the </span>central nervous system<span> (CNS) and is highly expressed in the rat hypothalamus, in particular the medial preoptic area and the </span></span>arcuate nucleus<span><span>. The mammalian bombesin family of receptors consists of three closely related </span>G protein coupled receptors, BB</span></span>₁, BB₂ and BB₃. The BB₁<span> receptor subtype has the highest affinity for NMB.</span></p><p><span>NMB has well documented roles in the regulation of the thyroid axis and the stress axis in rats. However, there is little available data regarding the role of NMB in the regulation of the hypothalamic–pituitary–gonadal (HPG) axis. It is known that the NMB receptor is expressed in immortalised gonadotrophin releasing hormone (GnRH) releasing GT1-7 cells and murine forebrain GnRH neurons, and that </span>anterior pituitary NMB-immunoreactivity is altered by changes in the sex steroid environment. The objective of these studies was thus to further investigate the effects of NMB on the HPG axis.</p><p>Intracerebroventricular (ICV) administration of NMB (10<!--> <span>nmol) to adult male rats significantly increased plasma luteinising hormone (LH) levels 30</span> <!-->min after injection (plasma LH ng/ml; saline 0.69<!--> <!-->±<!--> <!-->0.07, 10<!--> <!-->nmol NMB 1.33<!--> <!-->±<!--> <!-->0.17, P<!--> <!-->&lt;<!--> <span>0.01). In vitro, NMB stimulated GnRH release from hypothalamic explants from male rats and from hypothalamic GT1-7 cells. NMB had no significant effect on LH release from anterior pituitary explants from male rats, or from pituitary LβT2 cells in vitro.</span></p><p>These results suggest a previously unreported role for NMB in the stimulation of the HPG axis via hypothalamic GnRH. Further work is now required to determine the receptor mediating the effects of NMB on the reproductive axis and the physiological role of NMB in reproduction.</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"187 ","pages":"Pages 6-11"},"PeriodicalIF":0.0,"publicationDate":"2013-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.10.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31802626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastric distension activates NUCB2/nesfatin-1-expressing neurons in the nucleus of the solitary tract","authors":"Marion S. Bonnet ,&nbsp;Wassila Ouelaa ,&nbsp;Vanessa Tillement ,&nbsp;Jerôme Trouslard ,&nbsp;André Jean ,&nbsp;Bruno J. Gonzalez ,&nbsp;Guillaume Gourcerol ,&nbsp;Michel Dallaporta ,&nbsp;Jean-Denis Troadec ,&nbsp;Lourdes Mounien","doi":"10.1016/j.regpep.2013.10.001","DOIUrl":"10.1016/j.regpep.2013.10.001","url":null,"abstract":"<div><p><span>Brainstem<span> structures such as the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the </span></span>vagus nerve<span><span> (DMNX) are essential for the digestive function<span> of the stomach. A large number of neurotransmitters including </span></span>glutamate<span> and gamma-aminobutyric acid (GABA) are involved in the central control of gastric functions. However, the neuropeptidergic<span><span><span> systems implicated in this process remain undetermined. Nesfatin-1 was recently identified as a neuropeptide cleaved from the N-terminal part of NEFA/nucleobindin 2 precursor (NUCB2). Central administration of this neuropeptide inhibits food consumption and </span>gastroduodenal motility in rodents. Interestingly, the NTS and the DMNX contain a dense population of NUCB2/nesfatin-1 cell bodies. These observations led us to investigate the possible involvement of NUCB2/nesfatin-1 neurons in the brainstem neuronal pathways that modulate gastric functions. We observed an activation of NTS NUCB2/nesfatinergic neurons after gastric distention in rats. In addition, we found that several NTS NUCB2/nesfatinergic neurons were GABAergic. Finally, when fluorogold was injected at the stomach level, many retrogradely labeled neurons were observed in the DMNX which were also positive for NUCB2/nesfatin-1. Taken together, these observations suggest for the first time that NUCB2/nesfatin-1 neurons of the NTS are sensitive to </span>gastric distension and then may contribute to the satiety signal.</span></span></span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"187 ","pages":"Pages 17-23"},"PeriodicalIF":0.0,"publicationDate":"2013-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.10.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31802635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracerebroventricular injection of stresscopin-related peptide enhances cardiovascular function in conscious rats","authors":"Ri Jin ,&nbsp;Mei-Zi Li ,&nbsp;Yan-Hua Bing ,&nbsp;Ri-Long Piao ,&nbsp;Ying-Jun Li ,&nbsp;Qing-Hua Jin ,&nbsp;De-Lai Qiu ,&nbsp;Hiroshi Kannan ,&nbsp;Chun-Ping Chu","doi":"10.1016/j.regpep.2013.07.001","DOIUrl":"10.1016/j.regpep.2013.07.001","url":null,"abstract":"<div><p><span>Stresscopin-related peptide (SRP), which is a member of the corticotropin-releasing factor (CRF) family, is a high-affinity ligand for the type 2 corticotropin-releasing factor receptor (CRF-R2) and is involved in stress-coping responses. Central treatment with SRP suppresses food intake, delays gastric emptying and decreases heat-induced edema, but the effects of central administration of SRP on the cardiovascular system are unclear. Here we examined the effects of intracerebroventricular (i.c.v.) administration of SRP on cardiovascular function, and compared the cardiovascular effects<span> of SRP and stresscopin (SCP). Our results showed that i.c.v. administration of SRP (0.5</span></span> <span><span>nmol) increased mean arterial blood pressure (MABP) and heart rate (HR), but failed to increase plasma </span>norepinephrine and epinephrine levels. Compared with an equivalent dose of SCP, the area under the curve (AUC) values for the changes in MABP and HR were significantly smaller with SRP, indicating that the cardiovascular effects of SRP were weaker than those mediated by SCP. Pre-treatment with a selective CRF-R2 antagonist, antisauvagine-30 (4</span> <!-->nmol, i.c.v.) abolished the SRP and SCP induced changes in MABP and HR. These results indicate that central administration of SRP induces a weaker enhancement of cardiovascular function through CRF-R2 than that induced by SCP and that these effects are mediated without increasing plasma norepinephrine and epinephrine levels.</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"186 ","pages":"Pages 7-11"},"PeriodicalIF":0.0,"publicationDate":"2013-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.07.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31577527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes","authors":"Bing Li ,&nbsp;Chen Luo ,&nbsp;Subrata Chowdhury ,&nbsp;Zu-Hua Gao ,&nbsp;Jun-Li Liu","doi":"10.1016/j.regpep.2013.07.005","DOIUrl":"10.1016/j.regpep.2013.07.005","url":null,"abstract":"<div><p>Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis. Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis. We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition. To test this possibility, Parp1<!--> <span>−/− and wild-type mice were injected with streptozotocin<span> to induce diabetes. Separately, acute pancreatitis was induced with repeated injections of caerulein. Upon streptozotocin administration, Parp1</span></span> <span><span>−/− mice displayed much decreased hyperglycemia<span> and preserved serum insulin level. The treatment induced similar levels of </span></span>Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1</span> <span><span>−/− mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation. In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion. Our results reconfirmed the protective effect of Parp1 </span>gene deletion on islet β-cells but questioned its effect on the acinar cells. In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.</span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"186 ","pages":"Pages 83-91"},"PeriodicalIF":0.0,"publicationDate":"2013-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.07.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31664496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Keratinocytes express cytokines and nerve growth factor in response to neuropeptide activation of the ERK1/2 and JNK MAPK transcription pathways","authors":"Xiaoyou Shi ,&nbsp;Liping Wang ,&nbsp;J. David Clark ,&nbsp;Wade S. Kingery","doi":"10.1016/j.regpep.2013.08.001","DOIUrl":"10.1016/j.regpep.2013.08.001","url":null,"abstract":"<div><p><span><span>Sensory neurons innervating the skin can release </span>neuropeptides<span> that are believed to modulate cellular proliferation<span><span>, wound healing, pigmentation<span>, and keratinocyte innate immune responses. While the ability of neuropeptides to stimulate keratinocyte production of inflammatory mediators has been demonstrated, there is no information concerning the mechanisms by which neuropeptide activation of keratinocyte </span></span>cell surface receptors ultimately leads to the up-regulation of mediator production. In this study we used a keratinocyte cell line to identify the presence of substance P (SP) and calcitonin gene-related peptide (CGRP) receptors on keratinocytes and examined the effects of SP and CGRP stimulation on keratinocyte neuropeptide signaling, cell proliferation, and interleukin-1β (IL-1β), interleukin-6 (IL-6), </span></span></span>tumor necrosis factor α<span><span><span> (TNF-α), and nerve growth factor (NGF) expression. Neuropeptide stimulation caused an up-regulation of neuropeptide </span>receptor expression in keratinocytes and a dramatic increase in keratinocyte secretion of SP and CGRP, suggesting possible autocrine or paracrine stimulatory effects and amplification of neuropeptide signaling. Both SP and CGRP concentration-dependently stimulated cellular proliferation and the expression and secretion of </span>inflammatory cytokines<span><span> and NGF in keratinocytes. SP also activated all 3 families of mitogen activated protein kinase<span> (MAPK) and nuclear factor κB (NFκB) in keratinocytes, while CGRP only activated p38 and extracellular signal related kinase1/2 (ERK1/2) MAPKs. Neuropeptide stimulated inflammatory mediatory production in keratinocytes was reversed by ERK1/2 and JNK inhibitors. The current study is the first to observe; 1) that CGRP stimulates keratinocyte expression of CGRP and its receptor complex, 2) that SP and CGRP stimulate IL-6 and TNF-α secretion in keratinocytes, 3) that SP activated all three MAPK families and the NFκB transcriptional </span></span>signaling pathway in keratinocytes, and 4) that SP and CGRP stimulated inflammatory mediator production in keratinocytes is dependent on ERK1/2 and JNK activation. These studies provide evidence suggesting that disruption of ERK1/2 and JNK signaling may potentially be an effective therapy for inflammatory skin diseases and pain syndromes mediated by exaggerated sensory neuron–keratinocyte signaling.</span></span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"186 ","pages":"Pages 92-103"},"PeriodicalIF":0.0,"publicationDate":"2013-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.08.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31668433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of exogenous vasoactive intestinal peptide on mesenteric lymph pathway during early intestinal ischemia–reperfusion injury in rats","authors":"Hui Yang ,&nbsp;Yu Jin ,&nbsp;Chun H. Wang ,&nbsp;Cheng W. Tang","doi":"10.1016/j.regpep.2013.06.014","DOIUrl":"10.1016/j.regpep.2013.06.014","url":null,"abstract":"<div><p>Mesenteric lymph pathway serves as the primary route by which gut injury leads to systemic inflammation and distant organ injury. The inflammation of the intestinal tract is partially mediated by vasoactive intestinal peptide (VIP). Therefore, the aim of this study was to test whether exogenous VIP affects mesenteric lymph pathway during early intestinal ischemia–reperfusion (IIR) injury. Rats were randomized into control, control<!--> <!-->+<!--> <!-->VIP, IIR and IIR<!--> <!-->+<!--> <!-->VIP groups. The observation of mesenteric lymph flow was carried out by cannulation of mesenteric lymphatics. The distribution of in vivo lymphocyte trafficking was performed by ⁵¹Cr labeled lymphocytes and was measured by γ-counter. Endotoxin concentration was assayed using the limulus test kit and TNF-α level was detected by ELISA. When IIR injury treated with VIP, the volumes of lymph flow increased by 80%, which caused the number of lymphocytes exiting in mesenteric lymphatic increased by 50% while the proportion of ⁵¹Cr-lymphocytes in Peyer's patches, intestinal effector tissues, mesenteric nodes, large intestine, stomach decreased by 58%, 51%, 58%, 63%, 64% respectively at the 6th h after reperfusion following intestinal ischemia. Meanwhile, endotoxin and TNF-α levels in intestinal lymph decreased by 51% and 83%. These results suggest that exogenous VIP ameliorates IIR induced splanchnic organ damage via inhibition of toxic mediators reaching systemic circulation and reinforcement of the effective immune responses in gut-associated lymphoid tissues (GALT).</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"186 ","pages":"Pages 36-42"},"PeriodicalIF":0.0,"publicationDate":"2013-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.06.014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31239022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DPP8 and DPP9 expression in cynomolgus monkey and Sprague Dawley rat tissues","authors":"Eric. B. Harstad ,&nbsp;Jonathan S. Rosenblum ,&nbsp;Mark D. Gorrell ,&nbsp;William E. Achanzar ,&nbsp;Lauro Minimo ,&nbsp;Jiangyue Wu ,&nbsp;Laura Rosini-Marthaler ,&nbsp;Russell Gullo ,&nbsp;Nicole D. Ordway ,&nbsp;Mark S. Kirby ,&nbsp;Kristina D. Chadwick ,&nbsp;Gregory N. Cosma ,&nbsp;Carolyn F. Moyer","doi":"10.1016/j.regpep.2013.07.003","DOIUrl":"10.1016/j.regpep.2013.07.003","url":null,"abstract":"<div><p><span>Dipeptidyl peptidases<span> (DPPs) are proteolytic enzymes that regulate many physiological systems by degrading </span></span>signaling peptides<span><span>. DPP8<span><span><span> and DPP9 are distinct from DPP4 in sequence, cellular localization and expression levels, thus implying distinct functions. However, DPP8 and DPP9 expression needs further delineation. We evaluated DPP4, DPP8 and DPP9 expression using three independent methods at the mRNA, protein, and functional levels to better understand the local physiological contribution of each </span>enzyme<span>. Sprague Dawley rats and </span></span>cynomolgus monkeys were selected for DPP4, DPP8 and DPP9 expression profiling to represent animal species commonly utilized for drug preclinical safety evaluation. A novel Xhibit assay of DPP protease activity was applied in addition to newly available antibodies for immunohistochemical localization. This combined approach can facilitate a functional evaluation of protease expression, which is important for understanding physiological relevance. Few inter-species differences were observed. Tissue mRNA and protein levels generally correlated to functional DPP4 and DPP8/9 </span></span>enzymatic activity<span>. All three proteins were seen in epithelial cells, lymphoid cells and some endothelial and vascular smooth muscle cells. Combined DPP8/DPP9 enzymatic activity was uniformly intracellular across tissues at approximately 10-fold lower levels than non-renal DPP4. Consistent levels of each DPP were detected among most non-renal tissues in rats and monkeys. DPP4 was ubiquitous, principally detected on cell membranes of epithelial and endothelial cells and was greatest in the kidney. The expression patterns suggest that DPP8 and DPP9 may act similarly across tissues, and that their actions might in part overlap with DPP4.</span></span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"186 ","pages":"Pages 26-35"},"PeriodicalIF":0.0,"publicationDate":"2013-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.07.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31578091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification, tissue distribution and regulation of preproghrelin in the brain and gut of Schizothorax prenanti","authors":"RongBin Wei,&nbsp;Tao Liu,&nbsp;ChaoWei Zhou,&nbsp;XingDong Zhang,&nbsp;DengYue Yuan,&nbsp;Tao Wang,&nbsp;FangJun Lin,&nbsp;Hu Chen,&nbsp;HongWei Wu,&nbsp;ZhiQiong Li","doi":"10.1016/j.regpep.2013.07.002","DOIUrl":"10.1016/j.regpep.2013.07.002","url":null,"abstract":"<div><p><span><span>Ghrelin is an important </span>gastrointestinal hormone involved in the regulation of feeding in both mammals and fish. In this study, the preproghrelin cDNA sequence was cloning in the gut of </span><em>Schizothorax prenanti</em> (<em>S. prenanti</em>). The preproghrelin gene, encoding 103-amino acids, was strongly expressed in the gut and brain using real-time quantitative RT-PCR (qPCR). The <em>S. prenanti</em> preproghrelin was detected in embryonic developmental stages. Further, it was detectable in unfertilized eggs, suggesting that ghrelin could be classified as maternal mRNA. An experiment was conducted to determine the expression profile of ghrelin during post-feeding and fasting status of the brain and gut. The results revealed a significant postprandial decrease in ghrelin mRNA expression in the gut 6<!--> <!-->h post-feeding (hpf) and brain (1.5 and 9<!--> <!-->hpf) compared to an unfed control group, indicating that food intake and processing affect the regulation of expression of ghrelin in <em>S. prenanti</em><span>. The constructed recombinant plasmid pMD-19</span> <!-->T-ghrelin was transformed to <em>Escherichia coli</em><span><span> BL21 and induced with IPTG, and the expressed product was identified by SDS-PAGE. The prokaryotic expression vector for ghrelin was constructed successfully, and </span>fusion protein was expressed in </span><em>E. coli</em> BL21, which laid the foundation for the further study on the function of this protein and its mechanism. Overall, our results provide evidence for a highly conserved structure and biological actions of ghrelin in <em>S. prenanti</em>. Further studies are required to identify the tissue specific functions of ghrelin in <em>S. prenanti</em>.</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"186 ","pages":"Pages 18-25"},"PeriodicalIF":0.0,"publicationDate":"2013-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.07.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31578093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}