Abstract

This project is designed to monitor the occurrence and induction of multiple forms of microsomal cytochrome P-450 at various ages in rabbits. Four forms of hepatic microsomal cytochrome P-450 have been isolated and characterized. Properties of these cytochromes such as immunoreactivity, molecular weights, and peptide fingerprinting can be used to distinguish each form and identify their occurrence in microsomes. Immunochemical techniques are being developed to provide quantitative information regarding the ontogenetic expression of each form and to localize the cytochromes in tissues histologically. These studies are designed to explore the relationship between the age-dependent occurrence of multiple forms of cytochrome P-450 and the balance between xenobiotic activation and detoxification catalyzed by the cytochromes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD004445-19
Application #
3310283
Study Section
Toxicology Study Section (TOX)
Project Start
1978-09-29
Project End
1989-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
19
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037

  Publications

Albertolle, Matthew E; Kim, Donghak; Nagy, Leslie D et al. (2017) Heme-thiolate sulfenylation of human cytochrome P450 4A11 functions as a redox switch for catalytic inhibition. J Biol Chem 292:11230-11242
Savas, Üzen; Wei, Shouzou; Hsu, Mei-Hui et al. (2016) 20-Hydroxyeicosatetraenoic Acid (HETE)-dependent Hypertension in Human Cytochrome P450 (CYP) 4A11 Transgenic Mice: NORMALIZATION OF BLOOD PRESSURE BY SODIUM RESTRICTION, HYDROCHLOROTHIAZIDE, OR BLOCKADE OF THE TYPE 1 ANGIOTENSIN II RECEPTOR. J Biol Chem 291:16904-19
Bumpus, Namandjé N; Johnson, Eric F (2011) 5-Aminoimidazole-4-carboxyamide-ribonucleoside (AICAR)-stimulated hepatic expression of Cyp4a10, Cyp4a14, Cyp4a31, and other peroxisome proliferator-activated receptor ?-responsive mouse genes is AICAR 5'-monophosphate-dependent and AMP-activated protein J Pharmacol Exp Ther 339:886-95
Hsu, Mei-Hui; Savas, Uzen; Lasker, Jerome M et al. (2011) Genistein, resveratrol, and 5-aminoimidazole-4-carboxamide-1-?-D-ribofuranoside induce cytochrome P450 4F2 expression through an AMP-activated protein kinase-dependent pathway. J Pharmacol Exp Ther 337:125-36
Savas, Uzen; Machemer, Daniel E W; Hsu, Mei-Hui et al. (2009) Opposing roles of peroxisome proliferator-activated receptor alpha and growth hormone in the regulation of CYP4A11 expression in a transgenic mouse model. J Biol Chem 284:16541-52
Hsu, Mei-Hui; Savas, Uzen; Griffin, Keith J et al. (2007) Human cytochrome p450 family 4 enzymes: function, genetic variation and regulation. Drug Metab Rev 39:515-38
Hsu, Mei-Hui; Savas, Uzen; Griffin, Keith J et al. (2007) Regulation of human cytochrome P450 4F2 expression by sterol regulatory element-binding protein and lovastatin. J Biol Chem 282:5225-36
Savas, Uzen; Hsu, Mei-Hui; Griffin, Keith J et al. (2005) Conditional regulation of the human CYP4X1 and CYP4Z1 genes. Arch Biochem Biophys 436:377-85
Savas, Uzen; Hsu, Mei-Hui; Johnson, Eric F (2003) Differential regulation of human CYP4A genes by peroxisome proliferators and dexamethasone. Arch Biochem Biophys 409:212-20
Cowart, L Ashley; Wei, Shouzuo; Hsu, Mei-Hui et al. (2002) The CYP4A isoforms hydroxylate epoxyeicosatrienoic acids to form high affinity peroxisome proliferator-activated receptor ligands. J Biol Chem 277:35105-12

Showing the most recent 10 out of 41 publications