Head injury and cytochrome P-450 enzymes. Differential effect on mRNA and protein expression in the Fischer-344 rat. 1993

S M Toler, and A B Young, and C J McClain, and S I Shedlofsky, and A M Bandyopadhyay, and R A Blouin
College of Pharmacy, Division of Pharmacology and Experimental Therapeutics, University of Kentucky, Lexington 40536-0082.

Head trauma produces debilitating injuries that affect millions of people each year. Such injuries lead to a cascade of physiologic sequelae resulting in a hypercatabolic/hypermetabolic state. Current information describing changes in hepatic drug metabolism as a result of head trauma is limited. In this study, the effect of craniotomy and craniotomy plus cerebral percussive injury (impact) were investigated and compared with anesthesia control. Steady-state mRNA levels for CYP2C11 and CYP3A were suppressed to 50% of control values 24 hr following injury for the impact treatments. Craniotomy treatments also demonstrated a 50% decline in steady-state levels of mRNA for CYP3A 24 hr following injury. However, Western blot analysis of the CYP3A enzyme revealed no change at 6, 24, or 48 hr following injury. In addition, activities for 2 alpha- and 6 beta-testosterone hydroxylase did not differ from control values at any time point. Spectral analysis of total P-450 demonstrated a very small decline of 15% for the impact treatment 48 hr following injury. Total cytochrome P-450 content did not differ from control values at any other time point. Head injury produces a profound decline in steady-state mRNA concentrations for CYP2C11 and CYP3A that do not translate into altered protein expression.

UI MeSH Term Description Entries
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D001930 Brain Injuries Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits. Brain Lacerations,Acute Brain Injuries,Brain Injuries, Acute,Brain Injuries, Focal,Focal Brain Injuries,Injuries, Acute Brain,Injuries, Brain,Acute Brain Injury,Brain Injury,Brain Injury, Acute,Brain Injury, Focal,Brain Laceration,Focal Brain Injury,Injuries, Focal Brain,Injury, Acute Brain,Injury, Brain,Injury, Focal Brain,Laceration, Brain,Lacerations, Brain
D003399 Craniotomy Surgical incision into the cranium. Craniectomy,Craniectomies,Craniotomies
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal

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