Disease relevance of Chgb

• Of the carcinoids, CgA was expressed in most of the tumors, except for the rectal and ovarian carcinoids, which expressed CgB strongly [1].
• We purified from pheochromocytoma chromaffin granules an SDS-PAGE 110-120 kDa protein whose N-terminal sequence matched that previously deduced from a human CgB cDNA [2].
• We conclude that CgB is extensively processed in glucagonoma tissue by limited proteolysis as prohormones at conserved basic residues [3].
• We examined CgA, SgI and SgII mRNA expression by reverse transcription-polymerase chain reaction in rat mammary adenocarcinoma and fibroadenoma which had arisen spontaneously in aging Fischer-344 rats [4].
• To investigate whether this sorting was due to coaggregation of the deletion mutant with endogenous granins, we expressed human CgB using recombinant vaccinia viruses, under conditions in which the synthesis of endogenous granins in the infected PC12 cells was shut off [5].

High impact information on Chgb

• Our results show that Piccolo is transported to nascent synapses on an approximately 80 nm dense core granulated vesicle together with other constituents of the active zone, including Bassoon, Syntaxin, SNAP-25, and N-cadherin, as well as chromogranin B [6].
• The disulfide-bonded loop of chromogranin B mediates membrane binding and directs sorting from the trans-Golgi network to secretory granules [7].
• The disulfide-bonded loop of chromogranin B (CgB), a regulated secretory protein with widespread distribution in neuroendocrine cells, is known to be essential for the sorting of CgB from the trans-Golgi network (TGN) to immature secretory granules [7].
• Sorting to ISG of full-length human CgB and a deletion mutant of human CgB (Deltacys-hCgB) lacking the 22-amino acid residues comprising the disulfide-bonded loop was compared in the rat neuroendocrine cell line PC12 [5].
• Upon transfection, i.e., with ongoing synthesis of endogenous granins, the sorting of the deletion mutant was only slightly impaired compared to full-length CgB [5].

Chemical compound and disease context of Chgb

• Transcriptional regulation of secretogranin II and chromogranin B by cyclic AMP in a rat pheochromocytoma cell line [8].

Biological context of Chgb

• With radioimmunoassay (RIA) and column chromatography, we first studied the processing of chromogranin B and secretogranin II during axonal transport [9].
• The determined amino acid sequence represents approximately 35% of the rat precursor CgB [3].
• Nucleotide sequence and cellular distribution of rat chromogranin B (secretogranin I) mRNA in the neuroendocrine system [10].
• Gene expression of enkephalin, chromogranin A, chromogranin B, and secretogranin II and their respective peptide products were studied with in situ hybridization and radioimmunoassays after daily oral administration of haloperidol, clozapine, risperidone, or zotepine for 21 days [11].
• Depolarization in the presence of BayK induced a strong up-regulation of the messages for chromogranin B, neuropeptide Y and VGF [12].

Anatomical context of Chgb

• Chromogranin B was mainly present in cholinergic motor neurons and large sensory neurons, and secretoneurin was restricted to adrenergic and sensory neurons [9].
• Chromogranin A was present in both ventral and dorsal roots, and chromogranin B was detected in ventral roots and in large sensory axons in the dorsal roots [9].
• In lizard, HA-IR endocrine cells were widely distributed from the oesophagus to the small intestine, but only those in the stomach co-stored CgA, CgB and SgII [13].
• Chromogranin-B (CgB), a secretory granule protein, is normally synthesized in a variety of neuroendocrine tissues, including the pancreatic islet alpha-cells [3].
• The mRNA of rat secretory-vesicle protein chromogranin B is abundant in brain, adrenal medulla, and anterior pituitary [10].

Associations of Chgb with chemical compounds

• Repeated phencyclidine treatment (10mg/kg/day) for five days resulted in elevated secretoneurin levels in cortical areas whereas chromogranin A and chromogranin B tissue levels were unchanged [14].
• Pre-treatment of rats with thiopental prior to kainic acid prevented seizures, the decline in catecholamines and the elevation of enkephalin and neuropeptide Y mRNAs but not that of chromogranin B [15].
• The relative composition of the secretory content (adrenaline vs noradrenaline and chromogranin A vs chromogranin B) changes at the end of the gestational period in parallel with the development of the corticosteroid-producing adrenal cortex [16].
• On the other hand, the peripherally acting ganglionic blocker chlorisondamine did not protect from the kainic acid-induced up-regulation of chromogranin B mRNA, suggesting that chromogranin B mRNA may be regulated by a direct effect of kainic acid on chromaffin cells [15].
• In PC-12 cells, DTT treatment caused a dramatic increase in unstimulated secretion of newly synthesized chromogranin B (CgB), presumably as a consequence of reducing the single conserved chromogranin disulfide bond (E. Chanat, U. Weiss, W. B. Huttner, and S. A. Tooze. EMBO J. 12: 2159-2168, 1993) [17].
• In resting cells, both insulin and chromogranin B were concentrated in the granule cores; upon stimulation, chromogranin B (but not insulin) was largely redistributed to the core periphery and the surrounding halo [18].

Regulatory relationships of Chgb

• Markedly increased levels of secretogranin II (125-160% of control) and chromogranin B (140-230% of control) mRNA were observed in granule cells of the dentate gyrus 0.5-2 h after amygdaloid stimulation-induced seizures [19].

Other interactions of Chgb

• Increased expression of CgB mRNA was delayed and prolonged compared with SgII and was significantly (P < 0.05) increased between 3 and 24 h (120-145%) after CSD, peaked at 2 days (180%), and was still elevated at 1 week (130%) compared with contralateral cortex [20].
• For the latter technique, the amounts of accumulation distal to the crush (presumably representing recycling and retrogradely transported peptides) were 30-40% of the amounts in the proximal accumulation for chromogranin A and secretoneurin, in contrast to chromogranin B, which showed 15% recycling [9].
• Insulin treatment induced increased levels of enkephalins, dopamine beta-hydroxylase, the amine carrier and of chromogranin B whereas catecholamines, cytochrome b-561 and chromagranin A remained slightly below control levels [21].
• Here we show that TGF-beta2 colocalizes with the trans-Golgi network marker TGN38 and a marker molecule for secretory granules, chromogranin B (CgB), in PC12 cells [22].
• The rat pituitary cell line GH4C1 secretes granins (chromogranin B and secretogranin II) and prolactin by the regulated secretory pathway [23].

Analytical, diagnostic and therapeutic context of Chgb

• Immunoblotting of neuroendocrine tissues (or their hormone storage vesicle cores) with both anti N-terminal and anti C-terminal CgB antisera suggested bidirectional cleavage or processing of CgB; in the anterior pituitary, a unique 40 kDa C-terminal fragment was observed [2].
• Eight peptides (fragments 1-8) purified by HPLC from acidic tumor extracts were partially sequenced and showed homology to CgB amino acid sequences deduced from rat, mouse, and human cDNA [3].
• Chromogranin B mRNA levels were not changed by either insulin treatment or hypophysectomy [24].
• Adrenal medullary chromogranin A messenger RNA levels in clipped rats were 3.2-fold higher (p = 0.029) than those in the control group, and chromogranin B messenger RNA levels were 4.6-fold higher (p = 0.05) [25].
• Immunohistochemistry performed in rat and bovine tissues established that chromogranin B is present in all cells of the adrenal medulla [26].

References