title: Peroxidized cholesterol-induced matrix metalloproteinase-9 activation and its suppression by dietary beta-carotene in photoaging of hairless mouse skin.
abstract: The activation of matrix metalloproteinase (MMP)-9 leading to the formation of wrinkle and sagging of skin is an essential step in the skin photoaging on exposure to ultraviolet A (UVA). This study attempted to elucidate the role of peroxidized cholesterol including cholesterol hydroperoxides (Chol-OOHs), primary products of lipid peroxidation in biomembranes, in MMP-9 activation and the effect of dietary beta-carotene in MMP-9 activation. Hairless mice were subjected to periodic UVA irradiation for 8 weeks. The amount of peroxidized cholesterol detected as total hydroxycholesterol in the skin was increased significantly by the exposure. The activity and protein level of MMP-9 were elevated with wrinkling and sagging formation. MMP-9 activity was also enhanced by the intracutaneous injection of Chol-OOHs into the mouse skin. Adding beta-carotene to the diet of the mice during the period of irradiation suppressed the activity and expression of MMP-9 as well as the wrinkling and sagging formation. The amount of cholesterol 5alpha-hydroperoxide, a singlet molecular oxygen oxygenation-specific peroxidized cholesterol, was significantly lowered by the addition of beta-carotene to the diet. These results strongly suggest that Chol-OOHs formed on exposure to UVA contribute to the expression of MMP-9, resulting in photoaging. Dietary beta-carotene prevents the expression of MMP-9, at least partly, by inhibiting photodynamic action involved in the formation of Chol-OOHs.
authors.affiliation: Department of Food Science, Graduate School of Nutrition and Bioscience, University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Minami
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kubo
authors.forename: Seiji
authors.initials: S
authors.lastname: Arase
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hirasaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nikawa
authors.forename: Noriko
authors.initials: N
authors.lastname: Bando
authors.forename: Yoshichika
authors.initials: Y
authors.lastname: Kawai
authors.forename: Junji
authors.initials: J
authors.lastname: Terao
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism* / Q000528:radiation effects; D051379:Mice; D008812:Mice, Hairless; D012867:Skin / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects* / Q000528:radiation effects*; D014466:Ultraviolet Rays; D024502:alpha-Tocopherol / Q000494:pharmacology; D019207:beta Carotene / Q000494:pharmacology*
chemical_list: D019207:beta Carotene; C002843:cholesterol hydroperoxide; D002784:Cholesterol; D020780:Matrix Metalloproteinase 9; D024502:alpha-Tocopherol