Abstract |
An enzymatic activity has been found in cytosolic preparations from mouse epidermis which catalyzes the formation of 8-hydroperoxyeicosatetraenoic acid/8-hydroxyeicosatetraenoic acid (8-HPETE/8-HETE) from arachidonate. In contrast to 12-lipoxygenase this enzyme activity was not detectable in normal (untreated) mouse skin but only after in vivo treatment with the phorbol ester tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate). The induction showed a maximum at 24 h after TPA treatment strictly depended on the age of the mice and the TPA dose and was prevented by cycloheximide. The primary product formed from arachidonic acid was 8-HPETE, and the enzyme seems not to possess a significant peroxidase activity. This result as well as studies with specific inhibitors and its cytosolic localization indicates this enzyme to be a member of the lipoxygenase family. Most of the 8-lipoxygenase activity is located in cells of the suprabasal compartment of the epidermis. In spite of being a cytosolic enzyme 8-lipoxygenase appeared to be lipophilic to some extent and was activated by lecithin. The enzyme did not require calcium ions or ATP and showed a pH optimum at 7.5-8.0. 8-HPETE/8-HETE levels in mouse epidermis in vivo were determined by gas chromatography-mass spectrometry and found to be strongly increased after phorbol ester treatment, in agreement with the induction of 8-lipoxygenase observed.
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Authors | G Fürstenberger, H Hagedorn, T Jacobi, E Besemfelder, M Stephan, W D Lehmann, F Marks |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 266
Issue 24
Pg. 15738-45
(Aug 25 1991)
ISSN: 0021-9258 [Print] United States |
PMID | 1874732
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Hydroxyeicosatetraenoic Acids
- Leukotrienes
- Liposomes
- Phosphatidylcholines
- 8-hydroperoxyeicosatetraenoic acid
- 8-hydroxyeicosatetraenoic acid
- Arachidonate Lipoxygenases
- arachidonate 8-lipoxygenase
- Tetradecanoylphorbol Acetate
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Topics |
- Aging
(metabolism)
- Animals
- Arachidonate Lipoxygenases
(metabolism)
- Catalysis
- Chromatography, Gas
- Chromatography, High Pressure Liquid
- Chromatography, Thin Layer
- Enzyme Activation
- Female
- Hydrogen-Ion Concentration
- Hydroxyeicosatetraenoic Acids
(biosynthesis, metabolism)
- Kinetics
- Leukotrienes
(biosynthesis, metabolism)
- Liposomes
- Mice
- Phosphatidylcholines
(metabolism)
- Skin
(drug effects, enzymology)
- Tetradecanoylphorbol Acetate
(pharmacology)
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