Skip to main content
Log in

Undegraded chromogranin A is present in serum and enters the endocytotic lysosomal pathway in kidney

  • Published:
Histochemistry Aims and scope Submit manuscript

Summary

Analysis of human and bovine serum by immunoblotting revealed the presence of the proprotein chromogranin A. By the same method chromogranin A was also found in rat, bovine and human kidney. However this organ did not contain any chromogranin A mRNA arguing against a synthesis within this organ. By immun-electron microscopy chromogranin A immunoreactivity was found in proximal tubule cells of rat kidney. Positive immunostaining was present in small vesicles within and in close proximity to the brush border and closer to the nucleus in typical lysosomal structures. These results make it likely that chromogranin A from serum reaches kidney tubule cells by glomerular filtration and is taken up into the endocytotic lysosomal pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Benedum UM, Baeuerle PA, Konecki DS, Frank R, Powell J, Mallet J, Huttner WB (1986) The primary structure of bovine chromogranin A: a representative of a class of acidic secretory proteins common to a variety of peptidergic cells. EMBO J 5:1495–1502

    Google Scholar 

  • Burnette WN (1981) ‘Western blotting’: electrophoretic transfer of proteins from sodium dodecyl sulfate polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem 112:195–203

    Google Scholar 

  • Cohn DV, Zangerle R, Fischer-Colbrie R, Chu LLH, Elting JJ, Hamilton JW, Winkler H (1982) Similarity of secretory protein I from parathyroid gland to chromogranin A from adrenal medulla. Proc Natl Acad Sci USA 79:6056–6059

    Google Scholar 

  • Falkensammer G, Fischer-Colbrie R, Richter K, Winkler H (1985) Cell-free and cellular synthesis of chromogranin A and B of bovine adrenal medulla. Neuroscience 14:735–746

    Google Scholar 

  • Fischer-Colbrie R, Frischenschlager I (1985) Immunological characterization of secretory proteins of chromaffin granules: chromogranins A, chromogranins B and enkephalin-containing peptides. J Neurochem 44:1854–1861

    Google Scholar 

  • Fischer-Colbrie R, Lassmann H, Hagn C, Winkler H (1985) Immunological studies on the distribution of chromogranin A and B in endocrine and nervous tissues. Neuroscience 16:547–555

    Google Scholar 

  • Fischer-Colbrie R, Schober M (1987) Isolation and characterization of chromogranins A, B, and C from bovine chromaffin granules and a rat pheochromocytoma. J Neurochem 48:262–270

    Google Scholar 

  • Galindo E, Rill A, Bader M-F, Aunis D (1991) Chromostatin, a 20-amino acid peptide derived from chromogranin A, inhibits chromaffin cell secretion. Proc Natl Acad Sci USA 88:1426–1430

    Google Scholar 

  • Geuze HJ, Slot JW (1980) Disproportional immunostaining patterns of two secretory proteins in guinea pig and rat exocrine pancreatic cells. An immunoferritin and fluorescence study. Eur J Cell Biol 21:93–100

    Google Scholar 

  • Greeley GH Jr, Thompson JC, Ishizuka J, Cooper CW, Levine MA, Gorr SU, Cohn DV (1989) Inhibition of glucose-stimulated insulin release in the perfused rat pancreas by parathyroid secretory protein-I (chromogranin-A). Endocrinology 124:1235–1238

    Google Scholar 

  • Helle KB (1966) Some chemical and physical properties of the soluble protein fraction of bovine adrenal chromaffin granules. Mol Pharmacol 2:298–310

    Google Scholar 

  • Hopwood D (1968) An immunohistochemical study of the adrenal medulla of the ox. A comparison of antibodies against whole ox chromaffin granules and ox chromogranin A. Histochemistry 13:323–330

    Google Scholar 

  • Hörtnagl H, Lochs H, Winkler H (1974) Immunological studies on the acidic chromogranins and on dopamine β-hydroxylase (E.C. 1.14.2.1) of bovine chromaffin granules. J Neurochem 22:197–199

    Google Scholar 

  • Hsiao RJ, Mezger MS, O'Connor DT (1990) Chromogranin A in uremia: Progressive retention of immunoreactive fragments. Kidney Int 37:955–964

    Google Scholar 

  • Iacangelo A, Affolter HU, Eiden LE, Herbert E, Grimes M (1986) Bovine chromogranin A: its sequence and the distribution of its messenger RNA in endocrine tissues. Nature 323:82–86

    Google Scholar 

  • Iacangelo A, Okayama H, Eiden LE (1988) Primary structure of rat chromogranin A and distribution of its mRNA. FEBS Lett 227:115–121

    Google Scholar 

  • Kilpatrick L, Gavine F, Apps D, Phillips J (1983) Biosynthetic relationship between the major matrix proteins of adrenal chromaffin granules. FEBS Lett 164:383–388

    Google Scholar 

  • Lassmann H, Hagn C, Fischer-Colbrie R, Winkler H (1986) Presence of chromogranin A, B and C in bovine endocrine and nervous tissues: a comparative immunohistochemical study. Histochem J 18:380–386

    Google Scholar 

  • Lloyd RV, Wilson BS (1983) Specific endocrine tissue marker defined by a monoclonal antibody. Science 222:628–630

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    Google Scholar 

  • Munoz DG, Kobylinski L, Henry DD, George DH (1990) Chromogranin A like immunoreactivity in the human brain — Distribution in bulbar medulla and cerebral cortex. Neuroscience 34:533–543

    Google Scholar 

  • Maunsbach AB (1969) Functions of lysosomes in kidney cells. In: Dingle JT, Fell HB (eds) Lysosomes, chapt. 4. North-Holland, Amsterdam, pp 115–149

    Google Scholar 

  • Nolan JA, Trojanowski J, Hogue-Angeletti R (1985) Neurons and neuroendocrine cells contain chromogranin: detection of the molecule in normal bovine tissues by immunochemical and immunohistochemical methods. J Histochem Cytochem 33:791–798

    Google Scholar 

  • O'Connor DT (1983) Chromogranin: widespread immunoreactivity in polypeptide hormone producing tissues and in serum. Regul Pept 6:263–280

    Google Scholar 

  • O'Connor DT, Bernstein KN (1984) Radioimmunoassay of chromogranin A in plasma as a measure of exocytotic sympathoadrenal activity in normal subjects and patients with pheochromocytoma. N Engl J Med 311:764–770

    Google Scholar 

  • O'Connor DT, Deftos LJ (1986) Secretion of chromogranin A by peptide-producing endocrine neoplasms. N Engl J Med 314:1145–1151

    Google Scholar 

  • O'Connor DT, Pandlan MR, Carlton E, Cervenka JH, Hsiao RJ (1989) Rapid radioimmunoassay of circulating chromogranin A: in vitro stability, exploration of the neuroendocrine character of neoplasia, and assessment of the effects of organ failure. Clin Chem 35:1631–1637

    Google Scholar 

  • Obendorf D, Schwarzenbrunner U, Fischer-Colbrie R, Laslop A, Winkler H (1988) Immunological characterization of a membrane glycoprotein of chromaffin granules: its presence in endocrine and exocrine tissues. Neuroscience 25:343–351

    Google Scholar 

  • Okayama H, Kawaichi M, Brownstein M, Lee F, Yokota T, Arai K (1987) High-efficiency cloning of full-length cDNA; construction and screening of cDNA expression libraries for mammalian cells. Methods Enzymol 154:3–28

    Google Scholar 

  • Rieker S, Fischer-Colbrie R, Eiden L, Winkler H (1988) Phylogenetic distribution of peptides related to chromogranins A and B. J Neurochem 50:1066–1073

    Google Scholar 

  • Rosa P, Hille A, Lee RWH, Zanini A, De Camilli P, Huttner WB (1985) Secretogranins I and II: two tyrosine-sulfated secretory proteins common to a variety of cells secreting peptides by the regulated pathway. J Cell Biol 101:1999–2011

    Google Scholar 

  • Schmid KW, Weiler R, Xu RW, Hogue-Angeletti R, Fischer-Colbrie R, Winkler H (1989) An immunological study on chromogranin A and B in endocrine and nervous tissues. Histochem J 21:365–373

    Google Scholar 

  • Schober M, Fischer-Colbrie R, Schmid KW, Bussolati G, O'Connor DT, Winkler H (1987) Comparison of chromogranins A, B, and secretogranin II in human adrenal medulla and pheochromocytoma. Lab Invest 57:385–391

    Google Scholar 

  • Schober M, Howe PR, Sperk G, Fischer-Colbrie R, Winkler H (1989) An increased pool of secretory hormones and peptides in adrenal medulla of stroke-prone spontaneously hypertensive rats. Hypertension 13:469–474

    Google Scholar 

  • Settleman J, Fonseca R, Nolan J, Hogue-Angeletti R (1985) Relationship of multiple forms of chromogranin. J Biol Chem 260:1645–1651

    Google Scholar 

  • Smith AD, Winkler H (1967) Purification and properties of an acidic protein from chromaffin granules of bovine adrenal medulla. Biochem J 103:483–492

    Google Scholar 

  • Smith WJ, Kirshner N (1967) A specific soluble protein from the catecholamine storage vesicles of bovine adrenal medulla. Purification and chemical characterization. Mol Pharmacol 3:52–62

    Google Scholar 

  • Sobol RE, O'Connor DT, Addison J, Suchocki K, Royston I, Deftos LJ (1986) Elevated serum chromogranin A concentrations in small-cell lung carcinoma. ann Intern Med 105:698–700

    Google Scholar 

  • Somogyi P, Hodgson AJ, De Potter RW, Fischer-Colbrie R, Schober M, Winkler H, Chubb IW (1984) chromogranin immunoreactivity in the central nervous system. Immunochemical characterization, distribution und relationship to catecholamine and enkephalin pathways. Brain Res Rev 8:193–230

    Google Scholar 

  • Steiner HJ, Weiler R, Ludescher C, Schmid KW, Winkler H (1990) Chromogranins A and B are co-localized with atrial natriuretic peptides in secretory granules of rat heart. J Histochem Cytochem 38:845–850

    Google Scholar 

  • Takiyyuddin MA, Baron AD, Cervenka JH, Barbosa JA, Neumann HPH, Parmer RJ, Sullivan PA, O'Connor DT (1991) Suppression of chromogranin-A release from neuroendocrine sources in man: pharmacological studies. J Clin Endocrinol Metab 72:616–622

    Google Scholar 

  • Tateishi K, Funakoshi A, Wakasugi H, Iguchi H, Shinozaki H, Abe M, Funakoshi S, Tamamura H, Yajima H, Matsuoka Y (1989) Plasma pancreastatin-like immunoreactivity in various diseases. J Clin Endocrinol Metab 69:1305–1308

    Google Scholar 

  • Tateishi K, Miyasaka K, Shinozaki H, Funakoshi S, Matsuoka Y, Funakoshi A (1990) Pancreastatin-like immunoreactivity in urine. J Clin Endocrinol Metab 71:842–845

    Google Scholar 

  • Tatemoto K, Efendic S, Mutt V, Makk G, Feistner GJ, Barchas JD (1986) Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature 324:476–478

    Google Scholar 

  • Tokuyasu KT (1980) Immunochemistry on ultrathin frozen sections. Histochem J 12:381–403

    Google Scholar 

  • Weiler R, Feichtinger H, Schmid KW, Fischer-Colbrie R, Grimelius L, Cedermark B, Papotti M, Bussolati G, Winkler H (1987) Chromogranin A and B and secretogranin II in bronchial and intestinal carcinoids. Virchows Arch [A] 412:103–109

    Google Scholar 

  • Weiler R, Marksteiner J, Bellmann R, Wohlfarter T, Schober M, Fischer-Colbrie R, Sperk G, Winkler H (1990) Chromogranins in rat brain: characterization, topographical distribution and regulation of synthesis. Brain Res 532:87–94

    Google Scholar 

  • Weiler R, Steiner H-J, Schmid KW, Obendorf D, Winkler H (1990) Glycoprotein II from adrenal chromaffin granules is also present in kidney lysosomes. Biochem J 272:87–92

    Google Scholar 

  • Winkler H, Apps DK, Fischer-Colbrie R (1986) The molecular function of adrenal chromaffin granules: established facts and unresolved topics. Neuroscience 18:261–290

    Google Scholar 

  • Woglfarter T, Fischer-Colbrie R, Hogue-Angeletti R, Eiden LE, Winkler H (1988) Processing of chromogranin A within chromaffin granules starts at C- and N-terminal cleavage sites. FEBS Lett 231:67–70

    Google Scholar 

  • Ziegler MG, Kennedy B, Morrissey E, O'Connor DT (1990) Norepinephrine clearance, chromogranin A and dopamine β-hydroxylase in renal failure. Kidney Int 37:1357–1362

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weiler, R., Steiner, H.J., Fischer-Colbrie, R. et al. Undegraded chromogranin A is present in serum and enters the endocytotic lysosomal pathway in kidney. Histochemistry 96, 395–399 (1991). https://doi.org/10.1007/BF00315996

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00315996

Keywords

Navigation