Review: Molecular Mechanism of Ultraviolet-Induced Keratinocyte Apoptosis

Publisher Website
Google Scholar
Abstract
This article reviews advances in the study of the molecular mechanisms for ultraviolet (UV)-induced keratinocyte apoptosis, with particular reference to the cytokines tumor necrosis factor- alpha (TNF-α) and Fas ligand (FasL). TNF-α and FasL induce their respective receptors and then activate caspase enzymes that are critically involved in the apoptotic process. This activation is further amplified by intracellular mitochondriaassociated mechanisms. Using gene-targeted knockout mice lacking either the TNF-Rp55 or the TNF-Rp75, we have shown that TNF-α plays an important role in UV-induced keratinocyte apoptosis via TNF-Rp55. TNF-Rp55 shares homology with Fas and contains an intracellular death domain. UV seems to directly stimulate cross-linking of Fas, resulting in the engagement of the death machinery. Fas-associated death domain protein (FADD) acts as an adapter protein in both the TNF-Rp55 and Fas death-inducing cascades and is responsible for downstream signal transduction by recruiting caspases. Moreover, signaling of p53 contributes to the induction of apoptosis by regulating Bcl-2 family expression and increasing surface Fas expression. In addition to induction mechanisms of apoptosis, there are numerous inhibitory molecules that play a role in restricting the apoptotic pathway. Thus, the ultimate determination of whether or not a cell undergoes apoptosis after UV radiation is based on the balance between agonist and antagonist pathways.