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Kinetic deuterium isotope effects in glucocorticoid receptor activation

Journal Article · · J. Receptor Res.; (United States)

Activation and deactivation of the chick thymus glucocorticoid receptor protein was studied in ordinary and heavy water by DNA-cellulose binding of the tritiated triamcinolone acetonide-receptor complex. Activation was significantly slower in heavy water if it was promoted by incubation at elevated temperature in buffers of low ionic strength. In the presence of 300 mM KC1 or after separation from the low molecular weight cytosol constituents, the complex was activated at the same rate in both solvents. Deactivation (time dependent loss of DNA-binding capacity) was much faster in ordinary than in heavy water regardless of gel filtration or the presence of KC1. A model of receptor activation-deactivation was constructed on the basis of these data that accounts for the observed kinetic deuterium isotope effects and reveals some submolecular details of the process.

Research Organization:
Semmelweis Univ. Medical School, Budapest, Hungary
OSTI ID:
5681666
Journal Information:
J. Receptor Res.; (United States), Journal Name: J. Receptor Res.; (United States) Vol. 4:1-6; ISSN JRERD
Country of Publication:
United States
Language:
English