Medicine and changing times.
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Family Practice↗
Biomedical subjects
A M Butler
Publications and source records attributed to A M Butler.
Hepatic biotransformation of parathion: role of cytochrome P450 in NADPH- and NADH-mediated microsomal oxidation in vitro.
In vitro studies have established that cytochrome P450 (P450) is deactivated by the electrophilic sulfur atom released during the enzymic oxidation of parathion to paraoxon. However, in vivo studies in rats have been unable to demonstrate significant P450 loss. This study evaluated the possibility that there may be alternate pathways of parathion biotransformation in liver, other than those mediated by P450 and supported by NADPH. Initial experiments confirmed that parathion administration did not decrease microsomal P450 or testosterone hydroxylation activities. Subsequent in vitro experiments identified an NADH-dependent pathway of parathion biotransformation, and MS was used to confirm that paraoxon and 4-nitrophenol were the products of both the NADH- and NADPH-dependent reactions. The Michaelis constants of the NADH-dependent formation of paraoxon and 4-nitrophenol (26 +/- 6 microM and 53 +/- 10 microM, respectively) were approximately 3-fold greater than those for the NADPH-supported reactions (9 +/- 1 microM and 18 +/- 3 microM, respectively). Induction of male rats with phenobarbital and dexamethasone, but not beta-naphthoflavone, produced similar increases in the rates of NADH- and NADPH-mediated parathion metabolism. Rates of NADH- and NADPH-dependent metabolism were highly correlated in linear relationships. An anti-NADPH-cytochrome P450 reductase (NADPH-P450 reductase) antibody partially inhibited microsomal parathion oxidation mediated by either cofactor, and the P450 inhibitor clotrimazole was similarly effective against the NADH- and NADPH-supported oxidation of parathion. Finally, a reconstituted system containing P450 2B1, NADPH-P450 reductase, and phospholipid supported parathion oxidation mediated by NADH.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Characterization of parvalbumin cDNA clones and gene expression in normal and dystrophic mice of strain 129 ReJ.
Parvalbumin is a calcium-binding protein found in fast-twitch skeletal muscles and selected cells in the brain. In several dystrophic mutants in the mouse, the parvalbumin content of skeletal muscles and brain is reduced and this deficiency appears to correlate with the inability of these mice to handle enhanced calcium uptake associated with the dystrophic process. In this study, two overlapping cDNA clones of 392 and 1268 base pairs were isolated from a mouse cDNA library in lambda gt11, characterized, and used as probes to study the involvement of the parvalbumin gene and its expression in various tissues of dystrophic mice of strain 129 ReJ. Southern blot analyses of restriction fragments of genomic DNA from normal and dystrophic mice indicate the same number and size of parvalbumin-specific gene fragments observed by other researchers, suggesting that the size of the Pva gene is the same in both normal and dystrophic mice of strain 129 ReJ. Northern blot analyses of total RNA from hind-limb muscles using cloned parvalbumin cDNA as probes revealed an abundant 800-nucleotide mRNA with lesser amounts of a 1000-nucleotide mRNA transcript in both normal and dystrophic mice of strain 129 ReJ. The amount of these mRNAs was reduced by 65-77% in dystrophic muscles preparations and was similar to the levels of beta-actin mRNA in these animals. These results suggest that parvalbumin gene expression is not down regulated in dystrophic mice of strain 129 ReJ.
Amino Acid Sequence↗