Biology:Chromogranin A
 Generic protein structure example |
Chromogranin A or parathyroid secretory protein 1 (gene name CHGA) is a member of the granin family of neuroendocrine secretory proteins. As such, it is located in secretory vesicles of neurons and endocrine cells such as islet beta cell secretory granules in the pancreas. In humans, chromogranin A protein is encoded by the CHGA gene.[1]
Tissue distribution
Examples of cells producing chromogranin A (ChgA) are chromaffin cells of the adrenal medulla, paraganglia, enterochromaffin-like cells and beta cells of the pancreas. It is present in islet beta cell secretory granules. chromogranin-A (CgA)+ Pulmonary neuroendocrine cells account for 0.41% of all epithelial cells in the conducting airway, but are absent from the alveoli.
Function
Chromogranin A is the precursor to several functional peptides including vasostatin-1, vasostatin-2, pancreastatin, catestatin and parastatin. These peptides negatively modulate the neuroendocrine function of the releasing cell (autocrine) or nearby cells (paracrine).
Chromogranin A induces and promotes the generation of secretory granules such as those containing insulin in pancreatic islet beta cells.
Clinical significance
Chromogranin A is elevated in pheochromocytomas.[2] It has been identified as autoantigen in type 1 diabetes.[3] A peptide fragment of ChgA located in the Vasostatin-1, namely ChgA29-42 has been identified as the antigenic epitope recognized by diabetogenic BDC2.5 T cells from type 1 diabetes prone NOD mice.[4][5]
It is used as an indicator for pancreas and prostate cancer[6] and in carcinoid syndrome.[7][8] It might play a role in early neoplasic progression. Chromogranin A is cleaved by an endogenous prohormone convertase to produce several peptide fragments. See chromogranin A GeneRIFs for references. In immunohistochemistry it can be used to identify a range of neuroendocrine tumours and is highly specific for both benign and malignant cells of this type.[9]
Mass spec data shows that several peptides originating from CHGA (163-194; 194–214; 272–295;) are significantly lower in samples from ulcerative colitis patients compared to control biopsies.[10]
There are considerable differences in the amino acid composition between different species' chromogranin A . Commercial assays for measuring human CGA can usually not be used for measuring CGA in samples from other animals. Some specific parts of the molecule have a higher degree of amino acid homology and methods where the antibodies are directed against specific epitopes can be used to measure samples from different animals.[11] Region-specific assays measuring defined parts of CGA, CGB and SG2 can be used for measurements in samples from cats and dogs.[12][13][14][15][16] In dogs, the catestatin concentration showed weak negative associations with left atrial and ventricular sizes and the catestatin concentration showed weak positive associations with blood pressure.[17]
Variants
Variants exist for pancreastatin in various populations of the world. The variant Glycine297Serine has been shown to be more potent in inhibiting insulin-induced glucose uptake, resulting in higher risk of insulin resistance and diabetes among carriers of this variant. A team of researchers led by the Indian Institute of Technology Madras has found that the Glycine297Serine variation was present in approximately 15 percent of Indian and other South Asian populations.[18] [19]
References
- ↑ "Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA". The Journal of Biological Chemistry 263 (23): 11559–63. August 1988. doi:10.1016/S0021-9258(18)37995-X. PMID 3403545.
- ↑ "High plasma levels of human chromogranin A and adrenomedullin in patients with pheochromocytoma". Tumori 91 (1): 53–8. 2005. doi:10.1177/030089160509100110. PMID 15850005.
- ↑ "Chromogranin A is an autoantigen in type 1 diabetes". Nature Immunology 11 (3): 225–31. March 2010. doi:10.1038/ni.1844. PMID 20139986.
- ↑ "Cutting edge: vasostatin-1-derived peptide ChgA29-42 is an antigenic epitope of diabetogenic BDC2.5 T cells in nonobese diabetic mice". Journal of Immunology 186 (7): 3831–5. April 2011. doi:10.4049/jimmunol.1003617. PMID 21357258.
- ↑ "Vasostatin-1 antigenic epitope mapping for induction of cellular and humoral immune responses to chromogranin A autoantigen in NOD mice". European Journal of Immunology 44 (4): 1170–80. April 2014. doi:10.1002/eji.201343986. PMID 24443235.
- ↑ "Elevated serum chromogranin A is detectable in patients with carcinomas at advanced disease stages". Annals of Clinical and Laboratory Science 30 (2): 175–178. April 2000. PMID 10807161.
- ↑ "Current diagnosis and treatment of gastrointestinal carcinoids in a series of 101 patients: the significance of serum chromogranin-A, somatostatin receptor scintigraphy and somatostatin analogues". Hepato-Gastroenterology 52 (63): 731–741. 2005. PMID 15966194.
- ↑ "Significance of chromogranin A and synaptophysin in pancreatic neuroendocrine tumors". Bosnian Journal of Basic Medical Sciences 20 (3): 336–346. August 2020. doi:10.17305/bjbms.2020.4632. PMID 32020844.
- ↑ Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd.. 2003. pp. 159–160. ISBN 1-84110-100-1.
- ↑ "Degradation of the extracellular matrix is part of the pathology of ulcerative colitis". Molecular Omics 15 (1): 67–76. February 2019. doi:10.1039/c8mo00239h. PMID 30702115.
- ↑ "Characterisation of N-terminal chromogranin A and chromogranin B in mammals by region-specific radioimmunoassays and chromatographic separation methods". The Journal of Endocrinology 165 (3): 703–14. June 2000. doi:10.1677/joe.0.1650703. PMID 10828855.
- ↑ "Chromogranins can be measured in samples from cats and dogs". BMC Research Notes 7 (1): 336. June 2014. doi:10.1186/1756-0500-7-336. PMID 24899097.
- ↑ "Chromogranin A and cortisol at intraoperative repeated noxious stimuli: Surgical stress in a dog model". SAGE Open Medicine 3: 2050312115576432. 27 March 2015. doi:10.1177/2050312115576432. PMID 26770773.
- ↑ "Catestatin, vasostatin, cortisol, temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale and visual analog scale for stress and pain behavior in dogs before and after ovariohysterectomy". BMC Research Notes 9 (1): 381. August 2016. doi:10.1186/s13104-016-2193-1. PMID 27484122.
- ↑ "Catestatin and vasostatin concentrations in healthy dogs". Acta Veterinaria Scandinavica 59 (1): 1. January 2017. doi:10.1186/s13028-016-0274-8. PMID 28049540.
- ↑ "Catestatin, vasostatin, cortisol, and visual analog scale scoring for stress assessment in healthy dogs". Research in Veterinary Science 117: 74–80. April 2018. doi:10.1016/j.rvsc.2017.11.015. PMID 29195227.
- ↑ "The chromogranin A-derived peptides catestatin and vasostatin in dogs with myxomatous mitral valve disease". Acta Veterinaria Scandinavica 62 (1): 43. August 2020. doi:10.1186/s13028-020-00541-3. PMID 32758260.
- ↑ "IIT Madras-led International Research Team Identifies gene/protein variation in Indians & other South Asians that increases risk of metabolic diseases". India Education Diary (Chennai). January 31, 2022. https://indiaeducationdiary.in/iit-madras-led-international-research-team-identifies-gene-protein-variation-in-indians-other-south-asians-that-increases-risk-of-metabolic-diseases/.
- ↑ "Functional Gly297Ser Variant of the Physiological Dysglycemic Peptide Pancreastatin is a Novel Risk Factor for Cardiometabolic Disorders". Diabetes 71 (3): 538–553. December 2021. doi:10.2337/db21-0289. PMID 34862200. (apparently the abstract has been released in advance of the full publication of the paper).
Further reading
- "Chromogranin A". Clinical and Investigative Medicine 18 (1): 47–65. February 1995. PMID 7768066.
- "Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway". Regulatory Peptides 58 (3): 65–88. August 1995. doi:10.1016/0167-0115(95)00069-N. PMID 8577930. https://zenodo.org/record/1258371.
- "WE-14, a chromogranin a-derived neuropeptide". Annals of the New York Academy of Sciences 971 (1): 311–6. October 2002. doi:10.1111/j.1749-6632.2002.tb04485.x. PMID 12438141. Bibcode: 2002NYASA.971..311C.
- "Isolation and primary structure of a novel chromogranin A-derived peptide, WE-14, from a human midgut carcinoid tumour". FEBS Letters 301 (3): 319–21. April 1992. doi:10.1016/0014-5793(92)80266-J. PMID 1577173.
- "Isolation and characterization of a tumor-derived human protein related to chromogranin A and its in vitro conversion to human pancreastatin-48". European Journal of Biochemistry 191 (1): 33–9. July 1990. doi:10.1111/j.1432-1033.1990.tb19090.x. PMID 2165909.
- "The primary structure of human chromogranin A and pancreastatin". The Journal of Biological Chemistry 262 (35): 17026–30. December 1987. doi:10.1016/S0021-9258(18)45486-5. PMID 2445752.
- "Isolation of human pancreastatin fragment containing the active sequence from a glucagonoma". FEBS Letters 228 (1): 153–6. February 1988. doi:10.1016/0014-5793(88)80606-9. PMID 2830133.
- "Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA". The Journal of Biological Chemistry 263 (23): 11559–63. August 1988. doi:10.1016/S0021-9258(18)37995-X. PMID 3403545.
- "Chromogranin from normal human adrenal glands: purification by monoclonal antibody affinity chromatography and partial N-terminal amino acid sequence". Regulatory Peptides 13 (3–4): 207–23. February 1986. doi:10.1016/0167-0115(86)90040-6. PMID 3704195. https://deepblue.lib.umich.edu/bitstream/2027.42/26277/1/0000362.pdf.
- "A cloned chromogranin A (CgA) cDNA detects a 2.3Kb mRNA in diverse neuroendocrine tissues". Biochemical and Biophysical Research Communications 137 (1): 418–23. May 1986. doi:10.1016/0006-291X(86)91226-X. PMID 3718511.
- "Chromogranin A, B, and C in human adrenal medulla and endocrine tissues". Laboratory Investigation; A Journal of Technical Methods and Pathology 55 (4): 405–11. October 1986. PMID 3762065.
- "The gene for human chromogranin A (CgA) is located on chromosome 14". Biochemical and Biophysical Research Communications 142 (1): 141–6. January 1987. doi:10.1016/0006-291X(87)90462-1. PMID 3814131. https://zenodo.org/record/1253796.
- "Chromostatin, a chromogranin A-derived bioactive peptide, is present in human pancreatic insulin (beta) cells". Proceedings of the National Academy of Sciences of the United States of America 90 (6): 2360–4. March 1993. doi:10.1073/pnas.90.6.2360. PMID 8096340. Bibcode: 1993PNAS...90.2360C.
- "Human chromogranin A gene. Molecular cloning, structural analysis, and neuroendocrine cell-specific expression". The Journal of Biological Chemistry 269 (9): 6918–26. March 1994. doi:10.1016/S0021-9258(17)37462-8. PMID 8120054.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Assignment of the chromogranin A (Chga) locus to homologous regions on mouse chromosome 12 and rat chromosome 6". Genomics 17 (1): 252–5. July 1993. doi:10.1006/geno.1993.1316. PMID 8406464.
- "Dispersion of chromogranin/secretogranin secretory protein family loci in mammalian genomes". Genomics 33 (1): 135–9. April 1996. doi:10.1006/geno.1996.0171. PMID 8617499.
- "Antibacterial activity of glycosylated and phosphorylated chromogranin A-derived peptide 173-194 from bovine adrenal medullary chromaffin granules". The Journal of Biological Chemistry 271 (45): 28533–40. November 1996. doi:10.1074/jbc.271.45.28533. PMID 8910482.
External links
- chromogranin A antibody stains via Google Image [1]
- Overview of all the structural information available in the PDB for UniProt: P10645 (Chromogranin-A) at the PDBe-KB.
- Overview of all the structural information available in the PDB for UniProt: P26339 (Mouse Chromogranin-A) at the PDBe-KB.
 |  |
