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Farid N Garas, Rahul S Shah, Eszter Kormann, Natalie M Doig, Federica Vinciati, Kouichi C Nakamura, Matthijs C Dorst, Yoland Smith, Peter J Magill, Andrew Sharott
Corticostriatal afferents can engage parvalbumin-expressing (PV+) interneurons to rapidly curtail the activity of striatal projection neurons (SPNs), thus shaping striatal output. Schemes of basal ganglia circuit dynamics generally consider striatal PV+ interneurons to be homogenous, despite considerable heterogeneity in both form and function. We demonstrate that the selective co-expression of another calcium-binding protein, secretagogin (Scgn), separates PV+ interneurons in rat and primate striatum into two topographically-, physiologically- and structurally-distinct cell populations...
2016: ELife
Seo-Yun Yang, Jae-Jin Lee, Jin-Hee Lee, Kyungeun Lee, Seung Hoon Oh, Yu-Mi Lim, Myung-Shik Lee, Kong-Joo Lee
Secretagogin (SCGN), a Ca(2+)-binding protein having six EF-hands, is selectively expressed in pancreatic β-cells and neuroendocrine cells. Previous studies suggested that SCGN enhances insulin secretion by functioning as a Ca(2+)-sensor protein, but the underlying mechanism has not been elucidated. The present study explored the mechanism by which SCGN enhances glucose-induced insulin secretion in NIT-1 insulinoma cells. To determine whether SCGN influences the first or second phase of insulin secretion, we examined how SCGN affects the kinetics of insulin secretion in NIT-1 cells...
June 15, 2016: Biochemical Journal
Qin Liu, Maode Lai
Secretagogin (SCGN) is a novel member of EF-hand Ca2+-binding proteins, which was identified in islet β cells by Wagner. SCGN is a six EF-hand Ca2+-binding protein, primarily expressed on the neuroendocrine axis and the central nervous system. The protein has abundant biological functions. A certain concentration of calcium ion can lead to conformation change of SCGN, resulting in the change of intracellular signal transduction. Preliminary studies showed that SCGN would be used to treat stress reaction, such as mental illness (depression), burns or post-traumatic stress disorder and chronic stress reaction caused by pain...
January 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
Fangying Xu, Qin Liu, Fengyan Han, Enping Xu, Maode Lai, Zhongsheng Zhao
OBJECTIVE: To investigate the association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma. METHODS: Clinicopathological data of 240 patients with gastric adenocarcinomas were retrospectively analyzed. The expression of chromogranin A, synaptophysin and secrectagogin in cancer tissue was assessed by immunohistochemistry. The association of neuoroendocrine differentiation parameters with disease progression and survival of patients was analyzed...
January 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
Masaki Kobayashi, Eiji Yamato, Koji Tanabe, Fumi Tashiro, Satsuki Miyazaki, Jun-ichi Miyazaki
Elucidating the regulation of glucose-stimulated insulin secretion (GSIS) in pancreatic β cells is important for understanding and treating diabetes. The pancreatic β cell line, MIN6, retains GSIS but gradually loses it in long-term culture. The MIN6 subclone, MIN6c4, exhibits well-regulated GSIS even after prolonged culture. We previously used DNA microarray analysis to compare gene expression in the parental MIN6 cells and MIN6c4 cells and identified several differentially regulated genes that may be involved in maintaining GSIS...
2016: PloS One
Orsolya Kántor, Szilvia Mezey, Jennifer Adeghate, Angela Naumann, Roland Nitschke, Anna Énzsöly, Arnold Szabó, Ákos Lukáts, János Németh, Zoltán Somogyvári, Béla Völgyi
Ca(2+)-buffer proteins (CaBPs) modulate the temporal and spatial characteristics of transient intracellular Ca(2+)-concentration changes in neurons in order to fine-tune the strength and duration of the output signal. CaBPs have been used as neurochemical markers to identify and trace neurons of several brain loci including the mammalian retina. The CaBP content of retinal neurons, however, varies between species and, thus, the results inferred from animal models cannot be utilised directly by clinical ophthalmologists...
July 2016: Cell and Tissue Research
Chuang Lyu, Jan Mulder, Swapnali Barde, Kristoffer Sahlholm, Hugo Zeberg, Johanna Nilsson, Peter Århem, Tomas Hökfelt, Kaj Fried, Tie-Jun Sten Shi
BACKGROUND: Increased nociceptive neuronal excitability underlies chronic pain conditions. Various ion channels, including sodium, calcium and potassium channels have pivotal roles in the control of neuronal excitability. The members of the family of G protein-gated inwardly rectifying potassium (GIRK) channels, GIRK1-4, have been implicated in modulating excitability. Here, we investigated the expression and distribution of GIRK1 and GIRK2 in normal and injured dorsal root ganglia (DRGs) and spinal cord of rats...
2015: Molecular Pain
Anand Kumar Sharma, Radhika Khandelwal, Yogendra Sharma, Vangipurapu Rajanikanth
Secretagogin (SCGN), a hexa EF-hand calcium-binding protein, is highly expressed in the endocrine cells (especially in pancreatic islets) and in restricted neuronal sub-populations, albeit at comparatively low level. Since SCGN is predicted to be a potential neuroendocrine marker in carcinoid tumors of lung and gastrointestinal tract, it is of paramount importance to understand the features of this protein in different environment for assigning its crucial functions in different tissues and under pathophysiological conditions...
May 2015: Protein Expression and Purification
Roman A Romanov, Alán Alpár, Ming-Dong Zhang, Amit Zeisel, André Calas, Marc Landry, Matthew Fuszard, Sally L Shirran, Robert Schnell, Árpád Dobolyi, Márk Oláh, Lauren Spence, Jan Mulder, Henrik Martens, Miklós Palkovits, Mathias Uhlen, Harald H Sitte, Catherine H Botting, Ludwig Wagner, Sten Linnarsson, Tomas Hökfelt, Tibor Harkany
A hierarchical hormonal cascade along the hypothalamic-pituitary-adrenal axis orchestrates bodily responses to stress. Although corticotropin-releasing hormone (CRH), produced by parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) and released into the portal circulation at the median eminence, is known to prime downstream hormone release, the molecular mechanism regulating phasic CRH release remains poorly understood. Here, we find a cohort of parvocellular cells interspersed with magnocellular PVN neurons expressing secretagogin...
January 2, 2015: EMBO Journal
Yifeng Bai, Yanqin Sun, Juan Peng, Hongzhan Liao, Hongyi Gao, Ying Guo, Linlang Guo
Secretagogin (SCGN) has recently been identified to play a crucial role in cell apoptosis, receptor signaling and differentiation. However, its clinical significance and functional roles in SCLC chemoresistance remain unknown. Here we examined the expression of SCGN in clinical samples from SCLC patients and evaluated its relation with clinical prognosis. Then up and down-regulation of SCGN were carried out in SCLC cell lines to assess its influence on chemoresistance. Furthermore, luciferase reporter assay was used to evaluate whether SCGN is a novel direct target of miR-494...
September 15, 2014: Oncotarget
Georgina Gáti, Dávid Lendvai, Tomas Hökfelt, Tibor Harkany, Alán Alpár
In the vertebrate nervous system, the Ca(2+)-binding proteins parvalbumin, calbindin and calretinin have been extensively used to elaborate the molecular diversity of neuronal subtypes. Secretagogin is a phylogenetically conserved Ca(2+)-binding protein, which marks neuronal populations largely distinct from other Ca(2+)-binding proteins in mammals. Whether secretagogin is expressed in nonmammalian vertebrates, particularly in birds, and, if so, with a brain cytoarchitectonic design different from that of mammals is unknown...
2014: Brain, Behavior and Evolution
Ming-Dong Zhang, Giuseppe Tortoriello, Brian Hsueh, Raju Tomer, Li Ye, Nicholas Mitsios, Lotta Borgius, Gunnar Grant, Ole Kiehn, Masahiko Watanabe, Mathias Uhlén, Jan Mulder, Karl Deisseroth, Tibor Harkany, Tomas G M Hökfelt
Neuronal calcium (Ca(2+))-binding proteins 1 and 2 (NECAB1/2) are members of the phylogenetically conserved EF-hand Ca(2+)-binding protein superfamily. To date, NECABs have been explored only to a limited extent and, so far, not at all at the spinal level. Here, we describe the distribution, phenotype, and nerve injury-induced regulation of NECAB1/NECAB2 in mouse dorsal root ganglia (DRGs) and spinal cord. In DRGs, NECAB1/2 are expressed in around 70% of mainly small- and medium-sized neurons. Many colocalize with calcitonin gene-related peptide and isolectin B4, and thus represent nociceptors...
March 25, 2014: Proceedings of the National Academy of Sciences of the United States of America
Katsuko Kosaka, Toshio Kosaka
Secretagogin (SCGN) is a recently discovered calcium binding protein of the EF hand family. We studied the structural features of SCGN-positive neurons in the mouse main olfactory bulb (MOB). SCGN-positive neurons were localized throughout layers but clustered in the glomerular layer (GL), mitral cell layer (MCL) and granule cell layer (GCL). They were heterogeneous, including numerous juxtaglomerular neurons, granule cells, small to medium-sized neurons in the external plexiform layer (EPL), and a few small cells in the ependymal/subependymal layer...
September 2013: Neuroscience Research
Felix Weltzien, Stefano Dimarco, Dario A Protti, Teresa Daraio, Paul R Martin, Ulrike Grünert
The retina contains at least 30 different types of amacrine cells but not many are well characterized. In the present study the calcium-binding protein secretagogin was localized in a population of regular and displaced amacrine cells in the retina of the common marmoset Callithrix jacchus. Irrespective of their soma location, the dendrites of secretagogin amacrine cells occupy strata 2, 3, and 4 of the inner plexiform layer, between the two bands formed by cholinergic amacrine cells. Segretagogin amacrine cells are also immunopositive to antibodies against glutamic acid decarboxylase, suggesting that they use γ-aminobutyric acid (GABA) as their neurotransmitter...
February 1, 2014: Journal of Comparative Neurology
Kazuhiro Hasegawa, Shu Wakino, Masumi Kimoto, Hitoshi Minakuchi, Keiko Fujimura, Koji Hosoya, Motoaki Komatsu, Yuka Kaneko, Takeshi Kanda, Hirobumi Tokuyama, Koichi Hayashi, Hiroshi Itoh
The role of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in glucose metabolism is unknown. Here, we generated DDAH2 transgenic (Tg) mice. These mice had lower plasma glucose levels (60 min: 298±32 vs. 418±35 mg/dl; 120 min: 205±15 vs. 284±20 mg/dl) and higher insulin levels (15 min: 2.1±0.2 vs. 1.5±0.1 ng/ml; 30 min: 1.8±0.1 vs. 1.5±0.1 ng/ml) during intraperitoneal glucose tolerance tests when fed a high-fat diet (HFD) compared with HFD-fed wild-type (WT) mice. Glucose-stimulated insulin secretion (GSIS) was increased in Tg islets by 33%...
June 2013: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Erika Gyengesi, Zane B Andrews, George Paxinos, Laszlo Zaborszky
Cholinergic and GABAergic corticopetal neurons in the basal forebrain play important roles in cortical activation, sensory processing, and attention. Cholinergic neurons are intermingled with peptidergic, and various calcium binding protein-containing cells, however, the functional role of these neurons is not well understood. In this study we examined the expression pattern of secretagogin (Scgn), a newly described calcium-binding protein, in neurons of the basal forebrain. We also assessed some of the corticopetal projections of Scgn neurons and their co-localization with choline acetyltransferase (ChAT), neuropeptide-Y, and other calcium-binding proteins (i...
May 2013: Brain Research Bulletin
Tie-Jun Sten Shi, Qiong Xiang, Ming-Dong Zhang, Giuseppe Tortoriello, Henrik Hammarberg, Jan Mulder, Kaj Fried, Ludwig Wagner, Anna Josephson, Mathias Uhlén, Tibor Harkany, Tomas Hökfelt
BACKGROUND: Secretagogin (Scgn), a member of the EF-hand calcium-binding protein (CaBP) superfamily, has recently been found in subsets of developing and adult neurons. Here, we have analyzed the expression of Scgn in dorsal root ganglia (DRGs) and trigeminal ganglia (TGs), and in spinal cord of mouse at the mRNA and protein levels, and in comparison to the well-known CaBPs, calbindin D-28k, parvalbumin and calretinin. Rat DRGs, TGs and spinal cord, as well as human DRGs and spinal cord were used to reveal phylogenetic variations...
2012: Molecular Pain
Aysegül Ilhan-Mutlu, Ludwig Wagner, Adelheid Wöhrer, Susanne Jungwirth, Christine Marosi, Peter Fischer, Matthias Preusser
BACKGROUND: There is little knowledge on blood alterations of glioblastoma. We had the opportunity to investigate markers from plasma taken 66, 36, and 6 months before glioblastoma in a patient in the VITA study. METHODS: We determined S100B, secretagogin, neuropeptide-Y, micro-RNA-21, let-7, micro-RNA-128, and micro-RNA-342-3p in our patient and 10 controls from VITA. RESULTS: We found a four-fold increase of micro-RNA-21 in the plasma of glioblastoma patient, whereas controls showed a significant decrease...
November 2012: Cancer Investigation
Wan Shun Daniel Tan, Jun Jie Lee, Ramapatna L Satish, Eng-Tat Ang
Secretagogin is a six EF-hand calcium-binding protein that can identify granule cells in the dentate gyrus of hippocampus. The aim of this study was to determine if secretagogin can be detected in human blood cells. Eight adult males were recruited for blood analysis. Whole blood was separated into plasma, peripheral mononuclear cells and erythrocytes with Ficoll-Paque and probed for secretagogin using reverse-transcription polymerase chain reaction and Western blot. While secretagogin mRNA was detected in both peripheral mononuclear cells and erythrocytes using reverse-transcription polymerase chain reaction, SCGN protein was only detected in erythrocytes...
September 20, 2012: Neuroscience Letters
Magdalena Maj, Ivan Milenkovic, Jan Bauer, Tord Berggård, Martina Veit, Aysegül Ilhan-Mutlu, Ludwig Wagner, Verena Tretter
Secretagogin is a calcium binding protein (CBP) highly expressed in neuroendocrine cells. It has been shown to be involved in insulin secretion from pancreatic beta cells and is a strong candidate as a biomarker for endocrine tumors, stroke, and eventually psychiatric conditions. Secretagogin has been hypothesized to exert a neuroprotective role in neurodegenerative diseases like Alzheimer's disease. The expression pattern of Secretagogin is not conserved from rodents to humans. We used brain tissue and primary neuronal cell cultures from rat to further characterize this CBP in rodents and to perform a few functional assays in vitro...
2012: Frontiers in Molecular Neuroscience
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