Mechanisms of ultraviolet light-induced pigmentation.
Work in the past 8 years, particularly in the past 1-2 years, has greatly expanded our understanding of the mechanisms by which ultraviolet irradiation stimulates melanogenesis in the skin. A direct effect of UV photons on DNA results in up-regulation of the gene for tyrosinase, the rate-limiting enzyme in melanin synthesis, as well as an increase in cell surface expression of receptors for at least one of the several known keratinocyte-derived melanogenic factors, MSH. Direct effects of UV on melanocyte membranes, releasing DAG and arachidonic acid, may also play a role in the tanning response. Diacylglycerol may activate PKC-beta, which in turn phosphorylates and activates tyrosinase protein; the pathways by which products of other inflammatory mediator cascades may act on melanogenesis are unknown. The tanning response also relies heavily on UV-stimulated increased production and release of numerous keratinocyte-derived factors including bFGF, NGF, endothelin-1 and the POMC-derived peptides MSH, ACTH, beta-LPH and beta-endorphin. These factors variably induce melanocyte mitosis, increase melanogenesis, enhance dendricity and prevent apoptotic cell death following the UV injury. Thus, events within the epidermal melanin unit conspire to maintain or increase melanocyte number, increase melanin pigment throughout the epidermis. Overall, ultraviolet-induced melanogenesis may be one part of a eukaryotic SOS response to damaging ultraviolet irradiation that has evolved over time to provide a protective tan in skin at risk of further injury from sun exposure. These recent insights into the mechanisms underlying ultraviolet-induced melanogenesis offer the opportunity for novel therapeutic approaches to minimizing acute and chronic photodamage in human skin.
Gilchrest
B A
BA
Department of Dermatology, Boston University School of Medicine, MA 02118-2394, USA.
Park
H Y
HY
Eller
M S
MS
Yaar
M
M
D002450:Cell Communication / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004789:Enzyme Activation; D006801:Humans; D008543:Melanins / Q000096:biosynthesis; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009414:Nerve Growth Factors / Q000502:physiology; D017785:Photons; D010858:Pigmentation / Q000235:genetics / Q000528:radiation effects*; D014466:Ultraviolet Rays
D008543:Melanins; D009414:Nerve Growth Factors; D014442:Monophenol Monooxygenase