DNA Photodamage Stimulates Melanogenesis and Other Photoprotective Responses

Abstract

Ultraviolet (UV) irradiation is a major source of environmental damage to skin. Melanin pigmentation protects against this damage by absorbing UV photons and UV-generated free radicals before they can react with DNA and other critical cellular components; and UV-induced melanogenesis or tanning is widely recognized as exposed skin's major defense against further UV damage. This article reviews extensive data suggesting DNA damage or DNA repair intermediates directly triggers tanning and other photoprotective responses. Evidence includes the observations that tanning is enhanced in cultured pigment cells by accelerating repair of UV-induced cyclobutane pyrimidine dimers or by treating the cells with UV-mimetic DNA-damaging chemicals. Moreover, small single stranded DNA fragments such as thymidine dinucleotides (pTpT), the substrate for almost all DNA photoproducts, also stimulates tanning when added to cultured pigment cells or applied topically to intact skin. In bacteria, single stranded DNA generated by DNA damage or its repair activates a protease that in turn derepresses over 20 genes whose protein products enhance DNA repair and otherwise promote cell survival, a phenomenon termed the SOS response. Interestingly, pTpT also enhances repair of UV-induced DNA damage in human cells and animal skin, at least in part by activating the tumor suppressor protein and transcription factor p53 and thus upregulating a variety of gene products involved in DNA repair and cell cycle regulation. Together, these data suggest that human cells have an evolutionarily conserved SOS-like response in which UV-induced DNA damage serves as signal to induce photoprotective responses such as tanning and increased DNA repair capacity. The responses can also be triggered in the absence of DNA damage by addition of small single-stranded DNA fragments such as pTpT.

Modifying skin pigmentation – approaches through intrinsic biochemistry and exogenous agents

“…As virtually all cells contain adenylate cyclase, attempts are now being made to develop agents that affect the melanogenic pathway more specifically. UVR not only stimulates αMSH secretion but it also causes DNA damage, and it is widely believed that such damage can itself induce tanning and DNA repair responses [86]. Damage to telomere loops at the ends of chromosomes and overhang exposure is considered to be a DNA damage signal [87].…”

Photoaging of human skin

“…This provides a rationale of why individuals with darker skin exhibit clinical signs of photoaging at much later stages than fair-skinned people (1). Induction of skin pigmentation by oligonucleotides containing thymine dinucleotide (pTpT) sequence motifs has been shown to protect from skin cancer-and photoaging-related features (18,19). Induction of skin pigmentation therefore may be one of the feasible strategies to protect skin from photoaging and will be discussed later in this review.…”

“…Work by Eller & Gilchrest indicated that oligonucleotides that contain thymine dinucleotides (pTpT) induce tanning of the skin (18). The presence of these pTpTs not only induced tanning of the skin but also provided protective effects against photocarcinogenesis and photoaging (19), providing a new and possibly powerful tool to improve the body's own ''sun-protection''.…”

Antimelanogenic effects of Inula britannica flower petal extract fermented by Lactobacillus plantarum KCCM 11613P

“…Melanin is known to be formed through the tyrosine pathway involving auto-oxidation and serves as a light-absorbing compound, which protects the skin against harmful ultraviolet (UV)-light (Gilchrest and Eller, 1999). Melanin synthesis is a complex process and requires numerous factors, including tyrosinase, autocrine and paracrine cytokines, tyrosinaserelated protein (TRP)-1, TRP-2, and other enzymes for melanin transportation and decomposition (Videira et al, 2013).…”