Functional aspects of eicosanoid hydroxylation by lung and kidney cytochromes P450. Expression of cDNAs in mammalian cells and E. coli.
A gene subfamily of cytochromes P450 with catalytic activity toward various eicosanoid substrates has been studied with a variety of techniques in this laboratory, including purification and characterization, localization at the tissue and subcellular levels, physiological function, and cloning and expression in prokaryotic and eukaryotic systems. This paper reports experiments directed toward determining the function of the cytochrome P4504A metabolite, 20-hydroxyarachidonic acid (20-hydroxyeicosatetraenoic acid; 20-HETE), in cellular ion flux, immunohistochemical localization in lung, the effects of a mechanism-based inhibitor, 12-hydroxy-16-heptadecynoic acid (12-HHDYA) on PGE1 omega-hydroxylation, and the structure-function determinants which govern the activities of the enzymes encoded by this gene subfamily.
Masters
B S
BS
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
Clark
J E
JE
Roman
L J
LJ
Nishimoto
M
M
McCabe
T J
TJ
Ortiz de Montellano
P R
PR
Plopper
C G
CG
Gebremedhin
D
D
Ma
Y H
YH
Harder
D R
DR
D000818:Animals; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D015777:Eicosanoids / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D011247:Pregnancy; D011817:Rabbits
D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A