A ZN(LL)-GLYCINE COMPLEX SUPPRESSES UVB-INDUCED MELANIN PRODUCTION BY STIMULATING METALLOTHIONEIN EXPRESSION.

Oxidative stress caused by ultraviolet (UV) radiation generates reactive oxygen species (ROS) in the skin, induces the secretion of melanocyte growth and activating factors from keratinocytes, which results in the formation of cutaneous hyperpigmentation. Thus, increasing the anti-oxidative ability of skin cells is expected to be a good strategy for skin-lightening cosmetics. Metallothionein (MT) is one of the stress-induced proteins and is known to exhibit a strong anti-oxidative property. We previously reported that a zinc(II) complex with glycine (Zn(II)(Gly)2) effectively induces MT expression in cultured human keratinocytes. To determine its potential as a new skin lightening active, we examined whether Zn(II)(Gly)2 regulates the release of melanocyte-activating factors from UVB-irradiated keratinocytes and affects melanin production in a reconstructed human epidermal equivalent. Conditioned medium from UVB-irradiated keratinocytes accelerated rnelanocyte prolifer¬ation to 110%, and that increase could be prevented by pretreatment with Zn(II)(Gly)2. In addition, Zn(II)(Gly)2 significantly reduced both the production of prostaglandin E2 and proopiomelanocortin expression in UVB-irradiated keratinocytes. Zn(II)(Gly)2 also decreased melanin production in a reconstructed human epidermal equivalent. These results indicate that MT-induction in the epidermis effectively up-reguiates tolerance against oxidative stress and inhibits the secretion of melanocyte growth and activating factors from keratinocytes. Thus, Zn(II)(Gly)2 is a good candidate as a new skin-lightening active.

MEL-300-A, Melanin production, Metallothionein, Skin lightening

UVB, Zn(II)(Gly)2