Selective processing of chromogranin A in the different islet cells in human pancreas.
We studied the immunoreactivity of 12 different region-specific antibodies to the chromogranin A (CgA) molecule in the four major neuroendocrine cell types of the human pancreas by using double immunofluorescence techniques. The antibodies raised to the N-terminal and midportions of CgA showed, on the whole, stronger immunoreactivity than did the C-terminal antibodies, with a few exceptions. Often the immunoreactivity was stronger in glucagon cells. Insulin cells expressed immunoreactivity to all region-specific antibodies, but glucagon cells were nonreactive to two antibodies. Somatostatin cells reacted only with the C-terminal antibodies (amino acid sequences CgA 411-424), while PP cells were stained with four CgA region-specific antibodies between amino acid sequences 63-195. The cause of these differences may be that the CgA molecule is cleaved, partly masked, or partly translated from CgA mRNA. Microwave treatment improved only the staining with the CgA 361-372 antibodies, which indicates that masking is not the sole or entire cause. Our findings may indicate that the CgA molecule is cleaved in different ways in the various pancreatic endocrine cell types, giving rise to a variety of biologically functional fragments.
Departments of Genetics and Pathology, Unit of Pathology, University of Lisbon, Portugal.
G M
GM
Portela-Gomes
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Stridsberg
D000328:Adult; D000918:Antibody Specificity; D053379:Chromogranin A; D002864:Chromogranins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D013004:Somatostatin / Q000378:metabolism
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D007328:Insulin; D010446:Peptide Fragments; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D005934:Glucagon