scholarly journals The post-translational processing of chromogranin A in the pancreatic islet: involvement of the eukaryote subtilisin PC2

1994 ◽  
Vol 298 (3) ◽  
pp. 521-528 ◽  
Author(s):  
S D Arden ◽  
N G Rutherford ◽  
P C Guest ◽  
W J Curry ◽  
E M Bailyes ◽  
...  
Keyword(s):  
Secretory Granule ◽  
Pancreatic Islet ◽  
Pancreatic Beta Cells ◽  
Chromogranin A ◽  
Time Course ◽  
Deae Cellulose ◽  
Neuroendocrine Cells ◽  
Time Period ◽  
Sds Page

The post-translational processing of chromogranin A (CGA) and the nature of the enzyme(s) involved were investigated in rat pancreatic islet and insulinoma tissue. Pulse-chase radiolabelling experiments using sequence-specific antisera showed that the 98 kDa (determined by SDS/PAGE) precursor was processed to an N-terminal 21 kDa peptide, a C-terminal 14 kDa peptide and a 45 kDa centrally located peptide with a rapid time course (t1/2 approx. 30 min) after an initial delay of 30-60 min. The 45 kDa peptide was, in turn, converted partially into a 5 kDa peptide with pancreastatin immunoreactivity and a 3 kDa peptide with WE-14 immunoreactivity over a longer time period. Incubation of bovine CGA with rat insulinoma secretory-granule lysate produced peptides of 18, 16 and 40 kDa via intermediates of 65 and 55 kDa. N-terminal sequence analysis indicated that cleavage occurred at the conserved paired basic sites Lys114-Arg115 and Lys330-Arg331, suggesting that cleavage of the equivalent sites (Lys129-Arg130 and Lys357-Arg358) in the rat molecule produced the initial post-translational products observed in intact pancreatic beta-cells. The enzyme activity responsible for the cleavage of bovine CGA co-chromatographed on DEAE-cellulose with the type-2 proinsulin endopeptidase and with PC2 immunoreactivity. The type-1 enzyme (PC1/3) appeared inactive towards CGA. The requirement for Ca2+ ions and an acidic pH for conversion was consistent with the involvement of a member of the eukaryote subtilisin family, and the composition of the released peptides in pulse-chase and secretion studies suggested that conversion occurred in the secretory-granule compartment. The overall catalytic rate as well as the relative susceptibilities of the Lys114-Arg115 and Lys330-Arg331 sites to cleavage were affected by pH, suggesting that the ionic environment of the processing compartment may play a role in the differential processing of CGA which is evident in various neuroendocrine cells.

scholarly journals The role of chromogranin-A and its derived peptide, WE-14 in the development of type 1 diabetes mellitus

2015 ◽  
Vol 156 (5) ◽  
pp. 163-170
Author(s):  
Zoltán Herold ◽  
Péter Nagy ◽  
Attila Patócs ◽  
Anikó Somogyi
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Chromogranin A ◽  
Neuroendocrine Tumour ◽  
Secretory Granules ◽  
Neuroendocrine Cells ◽  
Diabetic Patients ◽  
Autoreactive Cells

Chromogranin-A is a member of the granine protein family. It is produced in neuroendocrine cells via secretory granules. Many cleavage proteins are formed from chromogranin-A, from which some have well known biological activity, while the function of others is not yet fully known. Serum chromogranin-A levels are used in neuroendocrine tumour diagnostics. Recent studies showed that one of its cleavage protein, WE-14 may also play a role in the development of type 1 diabetes. WE-14 may function as an autoantigen for T-cells involved in the destruction of β-cells. This mechanism was previously observed only in non-obese diabetic mice. Novel results show that WE-14 also serves as a target for autoreactive cells in newly diagnosed type 1 diabetic patients as well, which reaction can be increased with transglutaminase. In this paper the authors summarize the recent knowledge about chromogranin-A and its potential role in the pathomechanism of type 1 diabetes mellitus. Orv. Hetil., 2015, 156(5), 163–170.

UPTAKE OF OXYTOCIN IN TISSUES AFTER INTRAVENOUS ADMINISTRATION OF TRITIATED OXYTOCIN IN RATS

1969 ◽  
Vol 61 (3) ◽  
pp. 432-440 ◽  
Author(s):  
Ingvar Sjöholm ◽  
Gunnar Rydén
Keyword(s):  
Skeletal Muscle ◽  
Distribution Pattern ◽  
Intravenous Injection ◽  
Intravenous Administration ◽  
Time Course ◽  
Tritiated Water ◽  
Preferential Distribution ◽  
Time Period ◽  
Initial Uptake

ABSTRACT The distribution of oxytocin in the kidneys, liver, uterus and skeletal muscle of the rat was followed during 10 min after intravenous injection of tritium labelled oxytocin. Oxytocin was found to be taken up and degraded mainly in the kidneys and the liver. After 150 seconds no intact oxytocin could be detected in these organs. The time course of the distribution of the radioactivity in the liver and the skeletal muscle showed no noteworthy characteristics, whereas a different course was found in the kidneys and in the uterus. In the kidneys, the radioactivity increased continuously from 60 to 200 seconds after the injection, indicating an accumulation of oxytocin or its metabolites in the kidneys. In the uterus a high initial uptake was observed, followed by a decrease of the radioactivity from 60 to 100 seconds after the injection. This distribution pattern was specific to oxytocin, since the uptake of tritiated tyrosine and tritiated water was almost constant during the same time period. These findings may indicate a preferential distribution of oxytocin to the uterus.

Development of silent gastric carcinoid in a type 1 diabetic patient with primer hypothyreosis

2007 ◽  
Vol 148 (35) ◽  
pp. 1667-1671 ◽  
Author(s):  
Anikó Somogyi ◽  
Éva Ruzicska ◽  
Timea Varga ◽  
Károly Rácz ◽  
Géza Nagy
Keyword(s):  
Diabetic Patient ◽  
Chromogranin A ◽  
Gastric Carcinoid

Az 1-es típusú cukorbetegség gyakran társul egyéb autoimmun kórképekkel. A parietalis sejtellenes antitestek (PCA), melyek az 1-es típusú cukorbetegek mintegy 20%-ában megtalálhatók, autoimmun gastritis és anaemia perniciosa jelenlétére figyelmeztetnek. A PCA-k a gyomor-H + /K + ATP-ázt károsítják, és hypo-/achlorhydriát, hypergastrinaemiát okozhatnak. Ennek következtében az enterochromaffin-szerű (ECL) sejtek hyper-/dysplasiaja alakulhat ki, mely carcinoid gyomortumor kialakulására hajlamosít. Az ECL-sejtek hyperplasiájából fejlődő gyomorcarcinoidok az autoimmun gastritises vagy anaemia perniciosában szenvedő betegek 4–9%-ában alakulnak ki. A 29 éves, 6 éve 1-es típusú diabéteszben szenvedő, 8 éves kora óta primer hypothyreosis miatt pajzsmirigyhormon-szubsztitúcióban részesülő nőbetegünknél gyomorpanaszok miatt felső panendoszkópia és biopsziás vizsgálat történt. Az endoszkópia többszörös kicsi polipokat mutatott a fundus területén nonantral hypergastrinaemiás (A-típusú) atrophiás gastritissel. A parietalis sejtantitest-vizsgálat pozitív volt, a szérum-chromogranin-A koncentrációja (CgA) 289,7 ng/ml (norm: 98 ng/ml alatt), a TSH-szint 9,93 mIU/L volt. A szövettani vizsgálat carcinoid tumort igazolt. Octreotidterápiát követően parciális gastrectomiát végeztek. Műtét után a szérum-chromogranin-A-szint normalizálódott. A nonatral, többszörös polipok néma neuroendocrin tumort takarhatnak, melyek rendszerint lassan növekvő, benignus viselkedésű endokrin daganatok, de magas malignitású endokrin karcinómák is lehetnek. A specifikus szérum- vagy szöveti chromogranin-A (CgA) és egyéb endokrin tumorra utaló markerek mérésének elérhetővé válásával e tumorok könnyen felismerhetők lehetnek a klinikus számára.

scholarly journals Role of miR-24 in Multiple Endocrine Neoplasia Type 1: A Potential Target for Molecular Therapy

2021 ◽  
Vol 22 (14) ◽  
pp. 7352
Author(s):  
Francesca Marini ◽  
Maria Luisa Brandi
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Current Knowledge ◽  
Neuroendocrine Cells ◽  
Molecular Therapy ◽  
Multiple Cancer ◽  
Men1 Gene ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant inherited multiple cancer syndrome of neuroendocrine tissues. Tumors are caused by an inherited germinal heterozygote inactivating mutation of the MEN1 tumor suppressor gene, followed by a somatic loss of heterozygosity (LOH) of the MEN1 gene in target neuroendocrine cells, mainly at parathyroids, pancreas islets, and anterior pituitary. Over 1,500 different germline and somatic mutations of the MEN1 gene have been identified, but the syndrome is completely missing a direct genotype-phenotype correlation, thus supporting the hypothesis that exogenous and endogenous factors, other than MEN1 specific mutation, are involved in MEN1 tumorigenesis and definition of individual clinical phenotype. Epigenetic factors, such as microRNAs (miRNAs), are strongly suspected to have a role in MEN1 tumor initiation and development. Recently, a direct autoregulatory network between miR-24, MEN1 mRNA, and menin was demonstrated in parathyroids and endocrine pancreas, showing a miR-24-induced silencing of menin expression that could have a key role in initiation of tumors in MEN1-target neuroendocrine cells. Here, we review the current knowledge on the post-transcriptional regulation of MEN1 and menin expression by miR-24, and its possible direct role in MEN1 syndrome, describing the possibility and the potential approaches to target and silence this miRNA, to permit the correct expression of the wild type menin, and thereby prevent the development of cancers in the target tissues.

Pancreatic islet surface engineering with a starPEG-chondroitin sulfate nanocoating

2019 ◽  
Vol 7 (6) ◽  
pp. 2308-2316 ◽  
Author(s):  
Jingyi Yang ◽  
Shan Jiang ◽  
Yong Guan ◽  
Juan Deng ◽  
Shaofeng Lou ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Islet Transplantation ◽  
Pancreatic Islet ◽  
Surface Engineering ◽  
Therapeutic Options

Islet transplantation is one of the most promising therapeutic options that could restore euglycaemia in type 1 diabetic individuals.

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