8S-lipoxygenase products activate peroxisome proliferator-activated receptor alpha and induce differentiation in murine keratinocytes

Citation
Sj. Muga et al., 8S-lipoxygenase products activate peroxisome proliferator-activated receptor alpha and induce differentiation in murine keratinocytes, CELL GROWTH, 11(8), 2000, pp. 447-454
Citations number
26
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL GROWTH & DIFFERENTIATION
ISSN journal
10449523 → ACNP
Volume
11
Issue
8
Year of publication
2000
Pages
447 - 454
Database
ISI
SICI code
1044-9523(200008)11:8<447:8PAPPR>2.0.ZU;2-5
Abstract
To determine the function and mechanism of action of the 8S-lipoxygenase (8 -LOX) product of arachidonic acid, 8S-hydroxyeicosatetraenoic acid (8S-HETE ), which is normally synthesized only after irritation of the epidermis, tr ansgenic mice with 8-LOX targeted to keratinocytes through the use of a lor icrin promoter were generated. Histological analyses showed that the skin, tongue, and stomach of transgenic mice are highly differentiated, and immun oblotting and immunohistochemistries of skin showed higher levels of kerati n-1 expression compared with wild-type mice. The labeling index, however, o f the transgenic epidermis was twice that of the wild-type epidermis, Furth ermore, 8S-HETE treatment of wild-type primary keratinocytes induced kerati n-1 expression. Peroxisome proliferator activated receptor alpha (PPAR alph a) was identified as a crucial component of keratin-1 induction through tra nsient transfection with expression vectors for PPAR alpha, PPAR gamma, and a dominant-negative PPAR, as well as through the use of known PPAR agonist s, From these studies, it is concluded that 8S-HETE plays an important role in keratinocyte differentiation and that at least some of its effects are mediated by PPAR alpha.