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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
1992-3-24
|
| pubmed:abstractText |
12-Hydroxyeicosatetraenoic acid (12-HETE) is formed from arachidonic acid either by 12-lipoxygenase or by a cytochrome P450 monooxygenase. 12-Lipoxygenase is generally localized in the soluble cytosolic fraction, and the cytochrome P450 monooxygenase is a microsomal enzyme. In this study, 12-HETE biosynthesis and the regulation of 12-HETE biosynthesis by epidermal growth factor (EGF) in A431 cells were investigated. 12-HETE was biosynthesized from arachidonic acid by the microsomal fraction of A431 cells, but not by the cytosolic fraction. The formation of 12-HETE was inhibited by 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, and caffeic acid. Nordihydroguaiaretic acid at 10(-4) M and 5,8,11,14-eicosatetraynoic acid at 10(-5) M almost completely inhibited its formation. However, the formation of 12-HETE was not affected by the presence of an NADPH-generating system, carbon monoxide, or SKF 525A. The biosynthetic 12-HETE was analyzed by chiral stationary phase high performance liquid chromatography and was highly enriched in (12S)-HETE. We therefore concluded that the enzyme responsible for the formation of (12S)-HETE in the microsomes of A431 cells is a 12-lipoxygenase. The microsomal 12-lipoxygenase of A431 cells belongs to the "leukocyte-type" enzyme as determined by substrate specificity and enzyme kinetics studies. The microsomal 12-lipoxygenase oxygenated linoleic acid much faster than the cytosolic platelet 12-lipoxygenase and is a "self-catalyzed inactivation" enzyme. Treatment of cells with 50 ng/ml EGF significantly induced microsomal 12-lipoxygenase activity. The lag period for the expression of the stimulatory effect of EGF on 12-lipoxygenase activity was approximately 10 h. The stimulatory effect of EGF on 12-lipoxygenase activity was completely blocked by treatment with 35 microM cycloheximide, indicating a requirement for de novo protein biosynthesis. Furthermore, the presence of the endogenous inhibitor of 12-lipoxygenase (which masked (12S)-HETE biosynthesis in intact cells) was identified in the cytosolic fraction of A431 cells. The putative inhibitor was enzyme-selective. It inhibited the leukocyte-type 12-lipoxygenase, but not the "platelet-type" enzyme.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/12-Hydroxy-5,8,10,14-eicosatetraenoi...,
http://linkedlifedata.com/resource/pubmed/chemical/5,8,11,14-Eicosatetraynoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 12-Lipoxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Aspirin,
http://linkedlifedata.com/resource/pubmed/chemical/Caffeic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyeicosatetraenoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Indomethacin,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/NADP,
http://linkedlifedata.com/resource/pubmed/chemical/Nordihydroguaiaretic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/caffeic acid
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
25
|
| pubmed:volume |
267
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3657-66
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:1740418-12-Hydroxy-5,8,10,14-eicosatetraenoic Acid,
pubmed-meshheading:1740418-5,8,11,14-Eicosatetraynoic Acid,
pubmed-meshheading:1740418-Animals,
pubmed-meshheading:1740418-Arachidonate 12-Lipoxygenase,
pubmed-meshheading:1740418-Arachidonic Acid,
pubmed-meshheading:1740418-Aspirin,
pubmed-meshheading:1740418-Caffeic Acids,
pubmed-meshheading:1740418-Chromatography, High Pressure Liquid,
pubmed-meshheading:1740418-Chromatography, Thin Layer,
pubmed-meshheading:1740418-Cycloheximide,
pubmed-meshheading:1740418-Epidermal Growth Factor,
pubmed-meshheading:1740418-Humans,
pubmed-meshheading:1740418-Hydroxyeicosatetraenoic Acids,
pubmed-meshheading:1740418-Indomethacin,
pubmed-meshheading:1740418-Lipoxygenase Inhibitors,
pubmed-meshheading:1740418-Mice,
pubmed-meshheading:1740418-Microsomes,
pubmed-meshheading:1740418-NADP,
pubmed-meshheading:1740418-Nordihydroguaiaretic Acid,
pubmed-meshheading:1740418-Stereoisomerism,
pubmed-meshheading:1740418-Substrate Specificity,
pubmed-meshheading:1740418-Tumor Cells, Cultured
|
| pubmed:year |
1992
|
| pubmed:articleTitle |
Epidermal growth factor enhances a microsomal 12-lipoxygenase activity in A431 cells.
|
| pubmed:affiliation |
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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