Peroxidized cholesterol-induced matrix metalloproteinase-9 activation and its suppression by dietary beta-carotene in photoaging of hairless mouse skin.
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.
Minami
Yuko
Y
Department of Food Science, Graduate School of Nutrition and Bioscience, University of Tokushima, Tokushima 770-8503, Japan.
Kawabata
Kyuichi
K
Kubo
Yoshiaki
Y
Arase
Seiji
S
Hirasaka
Katsuya
K
Nikawa
Takeshi
T
Bando
Noriko
N
Kawai
Yoshichika
Y
Terao
Junji
J
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*
D019207:beta Carotene; C002843:cholesterol hydroperoxide; D002784:Cholesterol; D020780:Matrix Metalloproteinase 9; D024502:alpha-Tocopherol