Endocrinology, Vol 134, 2057-2063, Copyright © 1994 by Endocrine Society

ARTICLES

Processing of chromogranin A by bovine parathyroid secretory granules: production and secretion of N-terminal fragments

BM Drees and JW Hamilton
Calcium Endocrinology Laboratory, Veterans Affairs Medical Center, Kansas City, Missouri 64128.

Chromogranin A (CgA) is a glycoprotein located in the secretory granules of multiple neuroendocrine tissues, including the parathyroid gland. Although the function of CgA is not known, a role has been proposed for CgA as a prohormone for biologically active peptides. Using 3H-CgA as a substrate for bovine parathyroid secretory granule extracts, we demonstrate a precursor product relationship between intact CgA and multiple N-terminal fragments of CgA. N-terminal CgA fragments of mol wt 24, 26, and 33 k are generated in a time dependent manner in the presence of bovine parathyroid secretory granule enzymes. The generation of the 33 kilodalton (kDa) N-terminal CgA fragment is calcium dependent. In the presence of EDTA, intermediate CgA fragments of mol wt 36 and 45 are generated. The effect of EDTA is reversible with added calcium. Based on immunodetection on Western blots, the 26 kDa N-terminal fragment of CgA is secreted by bovine parathyroid cells in a time and calcium-dependent manner in parallel with PTH and intact CgA. The secretion of the 26 kDa N-terminal fragment of CgA increases in response to low calcium incubation conditions and is suppressed by high calcium incubation conditions. We conclude that bovine parathyroid secretory granules contain enzymatic activity capable of processing CgA to multiple N-terminal fragments. The secretion of at least one N- terminal fragment (26 kDa) is calcium responsive. The physiological significance of CgA processing in parathyroid secretory granules is as yet unknown.

This article has been cited by other articles:

				A. Dey, C. Norrbom, X. Zhu, J. Stein, C. Zhang, K. Ueda, and D. F. Steiner Furin and Prohormone Convertase 1/3 Are Major Convertases in the Processing of Mouse Pro-Growth Hormone-Releasing Hormone Endocrinology, April 1, 2004; 145(4): 1961 - 1971. [Abstract] [Full Text] [PDF]

				V. Turquier, H. Vaudry, S. Jégou, and Y. Anouar Frog Chromogranin A Messenger Ribonucleic Acid Encodes Three Highly Conserved Peptides. Coordinate Regulation of Proopiomelanocortin and Chromogranin A Gene Expression in the Pars Intermedia of the Pituitary During Background Color Adaptation Endocrinology, September 1, 1999; 140(9): 4104 - 4112. [Abstract] [Full Text]

				J. Ciesielski-Treska, G. Ulrich, L. Taupenot, S. Chasserot-Golaz, A. Corti, D. Aunis, and M.-F. Bader Chromogranin A Induces a Neurotoxic Phenotype in Brain Microglial Cells J. Biol. Chem., June 5, 1998; 273(23): 14339 - 14346. [Abstract] [Full Text] [PDF]

				G. N. Hendy, H. P. J. Bennett, B. F. Gibbs, C. Lazure, R. Day, and N. G. Seidah Proparathyroid Hormone Is Preferentially Cleaved to Parathyroid Hormone by the Prohormone Convertase Furin J. Biol. Chem., April 21, 1995; 270(16): 9517 - 9525. [Abstract] [Full Text] [PDF]

				C. V. Taylor, L. Taupenot, S. K. Mahata, M. Mahata, H. Wu, S. Yasothornsrikul, T. Toneff, C. Caporale, Q. Jiang, R. J. Parmer, et al. Formation of the Catecholamine Release-inhibitory Peptide Catestatin from Chromogranin A. DETERMINATION OF PROTEOLYTIC CLEAVAGE SITES IN HORMONE STORAGE GRANULES J. Biol. Chem., July 21, 2000; 275(30): 22905 - 22915. [Abstract] [Full Text] [PDF]