Stabilization of glucocorticoid receptors in isolated rat hepatocytes by radioprotectants
Previous work has shown that glucocorticoid receptors in rat liver homogenate can be stabilized by the addition of MoO/sub 4/ plus the sulfhydryl-containing compounds dithiothreitol and WR 1065. The latter is the dephosphorylated, principal metabolite of the radioprotectant WR 2721 (or S-2-(3-aminopropylamino)ethanesphosphorothioic acid). The current work results from applying this knowledge to intact rat hepatocytes. Cells were isolated by collagenase perfusion and incubated in supplemented minimum essential medium at 37/sup 0/C with various concentrations of WR 2721, WR 1065, or vehicle. Samples of these cell suspensions were analyzed at various times for steroid binding capacity by incubating homogenates (27,000 x g supernates) with 50 nM /sup 3/H-triamcinolone acetonide in the presence or absence of excess unlabelled dexamethasone. Concentrations of 10 mM WR 2721 provided marked preservation of the binding capacity (>85% of the initial value at 5 hours) compared to control at <20% by 2 hours. WR 2721 at 1 mM preserved >60% of the binding capacity. WR 1065 at 10 mM provided no such protection. This is consistent with the observation that WR 1065 does not pass cell membranes. The authors propose that supplying reducing equivalents to intracellular components such as the glucocorticoid receptor may be one mechanism of the radioprotection afforded by WR 2721.
- Research Organization:
- Walter Reed Army Institute of Research, Washington, DC
- OSTI ID:
- 6989308
- Report Number(s):
- CONF-8606151-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
GLUCOCORTICOIDS
BIOCHEMICAL REACTION KINETICS
RECEPTORS
RADIOPROTECTIVE SUBSTANCES
BIOLOGICAL EFFECTS
STABILIZATION
DEXAMETHASONE
HOMOGENATES
LIVER CELLS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ANIMAL CELLS
ANIMALS
CORTICOSTEROIDS
DRUGS
HORMONES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
PREGNANES
PROTEINS
REACTION KINETICS
RODENTS
SOMATIC CELLS
STEROID HORMONES
STEROIDS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques