Glucocorticoid regulation of amidating enzyme in a neoplastic C-cell line

doi:10.1016/0303-7207(89)90194-9

Molecular and Cellular Endocrinology

Volume 61, Issue 1, January 1989, Pages 109-116

https://doi.org/10.1016/0303-7207(89)90194-9 Get rights and content

Abstract

Posttranslationar carboxyl-terminal amidation of many peptides is accomplished by peptidylglycine α-amidating monooxygenase. We have previously demonstrated that glucocorticoids stimulate production of amidated products by the CA-77 rat medullary thyroid carcinoma cell line. The present investigation was undertaken to determine whether amidation enzyme activity changes in parallel.

Enzyme activity, similar to that found in other tissues, was readily detected in cell extracts and conditioned cultured medium. Stimulation with the calcitonin secretagogue calcium increased secretion of enzyme activity and lowered cell extract activity. Treatment of cultures with dexamethasone, but no other steroid, decreased by 50–70% the basal amidation enzyme activity secreted. There was no associated change in cellular activity. The decrease in medium activity was partially reversible and steroid-dose dependent. The glucocorticoid-induced change in medium activity was due to a decreased V_m. These experiments demonstrate that the a-amidating activity of the CA-77 cells can be hormonally regulated.

References (36)

R.S. Birnbaum et al.
J. Biol. Chem.
(1986)
P. Böhlen et al.
Arch. Biochem. Biophys.
(1973)
A.F. Bradbury et al.
Biochem. Biophys. Res. Commun.
(1983)
M.L. Brock et al.
Cell
(1983)
S.E. Carty et al.
J. Biol. Chem.
(1982)
D.J. Diamond et al.
J. Mol. Biol.
(1985)
B.A. Eipper et al.
J. Biol. Chem.
(1986)
S. Gomez et al.
FEES Lett.
(1984)
L. Hilsted et al.
FEBS Lett.
(1986)
B.N. Jones et al.
Anal. Biochem.
(1988)

V. May et al.

Endocrinology

(1985)

N.M. Mehta et al.

Arch. Biochem. Biophys.

(1988)

K. Mizuno et al.

Biochem. Biophys. Res. Commun.

(1986)

K. Mizuno et al.

Biochem. Biophys. Res. Commun.

(1987)

A.S.N. Murthy et al.

J. Biol. Chem.

(1986)

M. Muszynski et al.

J. Biol. Chem.

(1983)

K. Ohsuye et al.

Biochem. Biophys. Res. Commun.

(1988)

L.H. Ouafik et al.

Biochem. Biophys. Res. Commun.

(1986)

Cited by (6)

Comparison of peptidyl-glycine α-amidation activity in medullary thyroid carcinoma cells, pheochromocytomas, and serum
1991, Molecular and Cellular Endocrinology
With an assay based on the radioimmunological detection of the formation of the C-terminal amide function on a neuropeptide Y-like substrate, amidation enzyme activity with apparent M_r of 56,000 and 38, 000 was found in pheochromocytoma extracts. The larger molecular form of amidating enzyme was also expressed and secreted from medullary thyroid carcinoma cells in a dexamethasone-suppressible way. Serum contained high levels of amidating enzyme activity with no difference between normal subjects and patients with pheochromocytomas. However, the majority of the amidating activity in serum was of much larger size, M_r between 80 and 105,000, compared to that released from the endocrine cells. No major difference was found between the molecular forms of amidation enzyme from tissues and from serum either in respect of enzyme kinetics or in respect of requirements for the cofactors copper and ascorbate. The major serum forms of enzyme were relatively independent of exogenous copper; however, they could still be quenched by cobber chelating agents. It is concluded that the molecular weight forms of the amidating enzyme circulating in serum are much larger than the soluble enzyme stored and secreted from most endocrine tissues.
Immunocytochemical mapping of the amidating enzyme PAM in the developing and adult mouse lung
1999, Journal of Histochemistry and Cytochemistry
Differential regulation of peptide α-amidation by dexamethasone and disulfiram
1999, Molecular Pharmacology
Effect of secretagogues on components of the secretory system in AtT-20 cells
1990, Endocrinology
Glucocorticoids regulate peptidyl-glycine α-amidating monooxygenase gene expression in the rat hypothalamic paraventricular nucleus
1990, Molecular Endocrinology
Tissue-specific regulation of peptidyl-glycine α-amidating monooxygenase expression
1989, Endocrinology

View full text

Glucocorticoid regulation of amidating enzyme in a neoplastic C-cell line

Abstract

J. Biol. Chem.

Arch. Biochem. Biophys.

Biochem. Biophys. Res. Commun.

Cell

J. Biol. Chem.

J. Mol. Biol.

J. Biol. Chem.

FEES Lett.

FEBS Lett.

Anal. Biochem.

Endocrinology

Arch. Biochem. Biophys.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.