Disease relevance of Chga

• Here, we characterize a large natural fragment, corresponding to chromogranin A 79-431, that inhibits growth of both Gram-positive and Gram-negative bacteria [1].
• To explore stimulus-transcription coupling in pheochromocytoma cells, we studied the biosynthetic response of chromogranin A, the major soluble protein co-stored and co-released with catecholamines, to chromaffin cells' physiologic nicotinic cholinergic secretory stimulation [2].
• Given the importance of plasminogen activation in tissue invasion and remodeling, the interplay between CgA and plasmin could provide a novel mechanism for regulating fibroblast adhesion and function in neuroendocrine tumors [3].
• Isolation and primary structure of a novel chromogranin A-derived peptide, WE-14, from a human midgut carcinoid tumour [4].
• Interferon-alpha inhibits chromogranin A promoter activity in neuroendocrine pancreatic cancer cells [5].

High impact information on Chga

• Chromogranin A, an "on/off" switch controlling dense-core secretory granule biogenesis [6].
• We present evidence that regulation of dense-core secretory granule biogenesis and hormone secretion in endocrine cells is dependent on chromogranin A (CGA) [6].
• Stable transfection of CGA into a CGA-deficient pituitary cell line, 6T3, lacking a regulated secretory pathway, restored regulated secretion [6].
• Overexpression of CGA induced dense-core granules, immunoreactive for CGA, in nonendocrine fibroblast CV-1 cells [6].
• Downregulation of CGA expression in a neuroendocrine cell line, PC12, by antisense RNAs led to profound loss of dense-core secretory granules, impairment of regulated secretion of a transfected prohormone, and reduction of secretory granule proteins [6].

Chemical compound and disease context of Chga

• We conclude that secretory stimulation of pheochromocytoma cells also activates the biosynthesis of the major secreted protein (chromogranin A), that the activation is transcriptional, and that a small proximal domain, including the CRE box, is, at least in part, both necessary and sufficient to account for the positive response to nicotine [2].
• A marked reduction in CGA expression occurred in pheochromocytomas induced by technical grade pentachlorophenol, compared to the other three chemicals and the spontaneously occurring tumors [7].

Biological context of Chga

• Evaluation of a rat/mouse somatic cell hybrid panel indicated that chromogranin A is on rat Chromosome 6 [8].
• Cell type-specific gene expression in the neuroendocrine system. A neuroendocrine-specific regulatory element in the promoter of chromogranin A, a ubiquitous secretory granule core protein [9].
• Chromogranin B-induced secretory granule biogenesis: comparison with the similar role of chromogranin A [10].
• The chromogranin A gene was complex, its eight exons and seven introns spanning about 11 kilobase pairs [11].
• To better understand its functional domains, its evolutionary lineage, and the basis of its tissue-specific pattern of expression, we obtained a mouse chromogranin A cDNA and used it to isolate the chromogrannin A gene from the mouse genome [11].

Anatomical context of Chga

• Targeted ablation of the chromogranin a (Chga) gene: normal neuroendocrine dense-core secretory granules and increased expression of other granins [12].
• The acidic secretory protein chromogranin A universally occurs in amine and peptide hormone and neurotransmitter storage granules throughout the neuroendocrine system [9].
• In contrast, inhibition of CGA expression in PC12 cells by siRNA treatment decreased the IP(3)-induced Ca(2+) releases in the nucleus by 17%, while inhibition of CGB expression decreased the IP(3)-induced Ca(2+) releases in the nucleus by 55% [13].
• Here, we report that downregulation of CgA expression in vivo by expressing antisense RNA against CgA in transgenic mice led to a significant reduction in DCG formation in adrenal chromaffin cells [14].
• Chromogranin A deficiency in transgenic mice leads to aberrant chromaffin granule biogenesis [14].

Associations of Chga with chemical compounds

• However, the excretion of epinephrine, norepinephrine, and dopamine was significantly elevated in the Chga null mutants [12].
• Chromogranin A immunoblots revealed chromogranin A processing, from both the NH2 and COOH termini, in both wild-type AtT-20 and AtT-20 antisense PC1 cells [15].
• Microinjection of IP(3) into the nucleus of CGB-expressing NIH3T3 cells increased the IP(3)-dependent nuclear Ca(2+) mobilization approximately 3-fold, whereas in CGA-expressing cells it remained the same as that of control cells [13].
• Chromogranin A/secretory protein I (CgA) is a glycoprotein that is stored and released along with peptide hormones and neurotransmitters from several tissues, although its exact function is not known [16].
• Three peptides, which shared the same 173-194 chromogranin A sequence (YPGPQAKEDSEGPSQGPASREK) but differed in post-translational modifications, including O-glycosylation and tyrosine phosphorylation, were isolated [1].

Regulatory relationships of Chga

• Antisense PC1 specifically abolished regulated secretion of both chromogranin A and beta-endorphin in response to the usual secretagogue, corticotropin-releasing hormone [15].
• PACAP activated the endogenous chromogranin A gene by four- to fivefold [17].

Other interactions of Chga

• Analysis of the allele distribution in an interspecific mouse backcross by single-strand conformation polymorphism positioned the chromogranin A locus on Chromosome 12, between Igh-C and D12Pas1 [8].
• Chromogranin A is an acidic protein, stored and released with catecholamines, and is overexpressed in genetic hypertension [8].
• In each case (mouse, rat, and human), chromogranin A is in a conserved region with nearby markers including the immunoglobulin heavy chain locus [8].
• To address the role of the Hoxa3 gene in parathyroid organogenesis, we examined the third pharyngeal pouch development by immunohistochemistry (IHC) using the secretory protein (SP)-1/chromogranin A antiserum, which recognizes the parathyroid from its initial formation onward [18].
• After antisense PC1 induction, an approximately 66-kD chromogranin A NH2-terminal fragment as well as the parent chromogranin A molecule accumulated, while an approximately 50 kD NH2-terminal and an approximately 30 kD COOH-terminal fragment declined in abundance [15].

Analytical, diagnostic and therapeutic context of Chga

• Moreover, immunocytochemistry demonstrated a relative decrease of chromogranin A in processes (where regulated secretory vesicles accumulate) of AtT-20 cells overexpressing either PC1 or PC2 [15].
• Variability of the chromogranin A/chromogranin B ratio was seen by confocal immunofluorescence also among the cells of single clones and subclones and among the granules of single cells [19].
• In addition, reverse transcriptase polymerase chain reaction (RT-PCR) revealed presence of chromogranin A mRNA in the MCC-1 cell line [20].
• In AtT20 cells, electrophoretic mobility shift assays and factor-specific antibody supershifts showed that an oligonucleotide containing the chromogranin A CRE site formed a single, homogeneous protein-DNA complex containing the CRE-binding protein CREB [21].
• Human chromogranin A gene. Molecular cloning, structural analysis, and neuroendocrine cell-specific expression [22].

References