title: Photoprotection against UVAR: effective triterpenoids require a lipid raft stabilizing chemical structure.
abstract: UVA(Ultraviolet A)-induced gene expression is supposed to be a hallmark for inflammation, for immunosuppression and in long-term cancer formation. In previous studies, we have shown for keratinocytes that physiological doses of UVA radiation result in the upregulation of gene expression mediated by ceramide formation from sphingolipids/cholesterol-rich microdomains (rafts), which can be blocked by preloading keratinocytes with cholesterol or plant sterols. Here, we show that besides stigmasterol and ß-sitosterol, also sterols like 14-dehydroergosterol, ergosterol-peroxide and 29-norcycloartenol inhibit the UVA response. Moreover, we present evidence that natural material-derived triterpenoids such as oleanolic acid can abrogate UVA-induced gene expression by raft stabilization. This effect depends on the structure of the molecule, because its isomer ursolic acid also integrates within the rafts without inhibiting ceramide formation and upregulation of gene expression.
authors.affiliation: Caesar & Loretz GmbH, Hilden, Germany Institute of Pharmaceutical Biology, University of Duesseldorf, Duesseldorf, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Bayer
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
authors.forename: Ingo
authors.initials: I
authors.lastname: Felsner
authors.forename: Heidi
authors.initials: H
authors.lastname: Brenden
authors.forename: Zippora
authors.initials: Z
authors.lastname: Kohne
authors.forename: Rehab
authors.initials: R
authors.lastname: Walli
authors.forename: Tu N
authors.initials: TN
authors.lastname: Duong
authors.forename: Christine
authors.initials: C
authors.lastname: Götz
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Grether-Beck
mesh_terms: D002478:Cells, Cultured; D002518:Ceramides / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism; D010840:Phytosterols / Q000737:chemistry / Q000494:pharmacology; D013473:Sunscreening Agents / Q000737:chemistry / Q000494:pharmacology*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D002518:Ceramides; D010840:Phytosterols; D013473:Sunscreening Agents; D014315:Triterpenes