Clofibrate-induced increases in peroxisomal proteins: effect on synthesis, degradation, and mRNA activity
Thesis/Dissertation
·
OSTI ID:5247194
The effect of clofibrate on the polypeptide composition of peroxisomes was determined. A simple method was developed for the isolation of peroxisomes with a purity of 90-95% using sedimentation in a metrizamide gradient. The specific activities of HD did not change with clofibrate treatment so that the increases in enzyme activities are solely due to increases in protein amounts. The hepatic concentration of HD increased 63 times. The HD synthesis rate, as measured by the incorporation of (/sup 3/H)leucine, increased 74 times, so that the increase in the synthesis was sufficient to account for the increase in protein. Clofibrate caused no discernible change in the degradation rate of HD labeled with (/sup 14/C)bicarbonate. The half-life of HD was approximately 2 days. The translatable mRBA coding for HD increased 55 times. This value is not significantly different from the increase in HD protein or in HD synthesis. This observation was also true for several other peroxisomal proteins. Therefore, clofibrate causes an increase in the mRNA activity, which increases the synthesis of HD leading to an accumulation of protein and enzyme activity. The kinetics of the clofibrate-induced changes in HD synthesis rate, protein level, and enzymatic activity was analyzed using a simple model which included the half-lives of the drug, mRNA, and protein. The best fit of the model to the data gave an mRNA half-life of 10 hours and a protein half-life of 1.8 days, with no significant change by clofibrate.
- Research Organization:
- Rockefeller Univ., New York (USA)
- OSTI ID:
- 5247194
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL HALF-LIFE
BIOSYNTHESIS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
DECOMPOSITION
ENZYME ACTIVITY
ESTERS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LEUCINE
MATHEMATICAL MODELS
MESSENGER-RNA
MONOCARBOXYLIC ACIDS
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROPIONIC ACID
PROTEINS
PURIFICATION
REACTION KINETICS
RNA
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL HALF-LIFE
BIOSYNTHESIS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
DECOMPOSITION
ENZYME ACTIVITY
ESTERS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LEUCINE
MATHEMATICAL MODELS
MESSENGER-RNA
MONOCARBOXYLIC ACIDS
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROPIONIC ACID
PROTEINS
PURIFICATION
REACTION KINETICS
RNA
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS