Melanin Function in the Skin

[Kala]

Melanin Functions as Protection
Source: Dermatology Times
By: John Otrompke
Originally published: November 1, 2003
http://mediwire.healingwell.com/main...rticleID=76876

Chicago -- While scientists have stated for years that those persons with greater skin pigment are less prone to suffer from skin cancer, and experience the aging effects of the sun more slowly than those with less skin pigment, research produced at this year's L'Oreal Ethnic Hair and Skin Conference, held here Sept. 19-21, provide quantitative evidence of the effects of skin pigment on the molecular responses in human skin in-vivo to ultraviolet (UV) irradiation.

The differences in responses do indeed correspond with the degree of skin pigment, according to Dr. Trisha Daley, M.D., resident in the department of dermatology at theUniversity of Michigan. "Pigment acts as a physical barrier, blocking UV irradiation. Reports have varied that black epidermis is equivalent to a sun protection factor between 2 and 13," Dr. Daley said. Skin pigment protects against both skin cancer and photoaging. In the case of photocarcinogenesis, the direct toxic effects of UV irradiation on keratinocyte DNA, as evidenced by the formation of thymine dimers, can ultimately lead to skin cancer. However, thymine dimer formation is minimal and occurs only in the superficial epidermis in darkly pigmented persons after UV irradiation, Dr. Daley said. Photoaging is a result of, among other factors, increases in matrix metalloproteinases (MMPs) after UV exposure, which break down collagen. This leads to invisible solar scars. With continued UV exposure, these solar scars accumulate becoming visible, and are clinically seen as wrinkles. MMPs are found to increase to lesser proportions after UV exposure in those with darkly pigmented skin than in other persons, Dr. Daley said.

Dr. Daley reported the results of a study of 38 persons, stratified into two groups based on objective measurement of surface skin color. The first group was composed of persons with surface skin color that corresponded to skin phototypes I and II; the other group was composed of individuals with surface skin color corresponding to skin phototypes V and VI. The two groups were exposed to ultraviolet B light, two to eight minimal erythema dose equivalents of the lightly pigmented group. Skin biopsy findings confirmed that skin pigment, or melanin, functions as a form of protection against skin cancer and photoaging. Protection from DNA damage was evidenced by the formation of fewer thymine dimer positive cells and these cells occurring only in the superficial epidermis in darkly pigmented skin, in contrast to substantial numbers of thymine dimer positive cells throughout the epidermis and papillary dermis in lightly pigmented skin. The differences were even more vividly demonstrated in the process of photoaging.

"When ultraviolet light targets the skin and activates kinase signaling pathways, which then up-regulates nuclear transcription factors, such as AP-1, a complex of c-Fos and c-Jun, a number of genes are transcribed, including MMPs. MMPs have a role in remodeling the dermis, especially, collagen," Dr. Daley said. "MMP-1 cleaves collagen, while MMP-3 and MMP-9 further degrade collagen, after MMP-1 has done its initial work. We never get back the original healthy collagen matrix, because it was imperfectly repaired," she noted. Interestingly, the levels of MMPs (especially MMP-1) found in the two groups varied significantly. "We found a 2,000-fold difference in matrix metalloproteinase 1 mRNA levels between the lightly and the darkly pigmented groups at two minimal erythema dose equivalents of ultraviolet B light," Dr. Daley said. "There was a 190-fold difference when we looked at MMP-3, and a 2.9-fold difference for MMP-9," she said. Ultraviolet A light also produced similar results.