Cysteine regulates expression of cysteine dioxygenase and ?-glutamylcysteine
synthetase in cultured rat hepatocytes.
Kwon, Young Hye, and Martha H. Stipanuk.
Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853
APStracts 8:0028E, 2001.
Rat hepatocytes cultured for 3 days in basal medium expressed low levels of cysteine
dioxygenase (CDO) and high levels of ?-glutamylcysteine synthetase (GCS). When the
medium was supplemented with 2 mmol/l methionine or cysteine, CDO activity and
CDO protein increased by >10-fold and CDO mRNA increased by 1.5- or 3.2-fold. In
contrast, GCS activity decreased to 51 or 29% of basal, GCS-heavy subunit (GCS-HS)
protein decreased to 89 or 58% of basal, and GCS mRNA decreased to 79 or 37% of
basal for methionine or cysteine supplementation, respectively. Supplementation with
cysteine consistently yielded responses of greater magnitude than did supplementation
with an equimolar amount of methionine. Addition of propargylglycine to inhibit
cystathionine ?-lyase activity and, hence, cysteine formation from methionine prevented
the effects of methionine, but not those of cysteine, on CDO and GCS expression.
Addition of buthionine sulfoximine to inhibit GCS, and thus block glutathione synthesis
from cysteine, did not alter the ability of methionine or cysteine to increase CDO. GSH
concentration was not correlated with changes in either CDO or GCS-HS expression. The
effectiveness of cysteine was equivalent to or greater than that of its precursors (S-
adenosylmethionine, cystathionine, homocysteine) or metabolites (taurine, sulfate).
Taken together, these results suggest that cysteine itself is an important cellular signal for
upregulation of CDO and downregulation of GCS.
Received 5 October 2000; accepted in final form 26 January 2001
APS Manuscript Number E458-0.
Article publication pending Am J Physiol Endocrinol Metab
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 27 February 2001