Purification and Characterization of the Epidermal 8(S)Lipoxygenase

Abstract

Skin epidermis forms a vast source of arachidonic acid metabolites. In cells, arachidonic acid is esterified to phopspholipids. Once released from its intracellular stores, arachidonic acid serves as a substrate for different families of oxygenases such as the prostaglandinsynthases, the cytochrome P-450-dependent epoxygenases and the lipoxygenases. Regulation of eicosanoid biosynthesis occurs both at the level of arachidonic acid mobilization and conversion into eicosanoids (for a review see [1]). Eicosanoids play a critical role in skin tumor development in mice. A striking event seen among the multiple changes in epidermal arachidonic acid metbolism produced by the tumor-promoting phorbol ester TPA is the induction ofa cytosolic 8(S)-lipoxygenase (8-LOX) activity. The enzyme catayzes the conversion of free arachidonic acid to 8(S)-HPETE and of free linoleic acid to 9(S)-HPODE. 8-LOX inducton is restricted to the suprabasal compartment of the epidermis and depends on transcriptional activation and de novo protein synthesis. A constitutive overexpression of 8-LOX activity has been observed in papillomas (2).