A Zn(II)–glycine complex suppresses UVB‐induced melanin production by stimulating metallothionein expression

Abstract

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 hyper-pigmentation. 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 melanocyte proliferation to 110%, and that increase could be prevented by pre-treatment with Zn(II)(Gly)(2). In addition, Zn(II)(Gly)(2) significantly reduced both the production of prostaglandin E(2) 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-regulates 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.

Role of antioxidants in the skin: Anti-aging effects

“…Zn(II)-glycine, a coordinated compound of Zn 2+ and glycine, has A cell-membrane permeable inducer of metallothionein that protects against UVB-induced cell damage and suppresses IL-1a secretion and prostaglandin E2 synthesis in human normal keratinocytes [75]. In addition, Zn(II)-glycine not only reduces pro-MMP-1 production but it also reduces the MMP-1 in dermal fibroblasts induced by the conditioned medium of UVB-irradiated keratinocytes.…”

Shining Light on Skin Pigmentation: The Darker and the Brighter Side of Effects of UV Radiation†

“…UV-induced oxidative stress increases the production of ROS and in response to the accumulating ROS, keratinocytes release factors that act on melanocytes and induce hyperpigmentation. A potential target for cosmetic skin-lightening systems would be to increase the anti-oxidants (43). …”

Antioxidants and Skin Aging

“…In addition, ergothioneine suppresses the expression of MMP-1 protein in fibroblasts exposed to UVA by quenching 1 O 2 (Obayashi et al 2005). Zn(II)-glycine, a coordinated compound of Zn 2+ and glycine, which is a cellmembrane permeable inducer of metallothionein and GSH, protects against UVBinduced cell damage and also suppresses IL-1a secretion and prostaglandin E 2 synthesis in human keratinocytes (Ochiai et al 2008). In addition, Zn(II)-glycine reduces pro-MMP-1 production in dermal fibroblasts induced by the conditioned medium of UVB-irradiated keratinocytes.…”