Ultraviolet light triggers the conversion of Cu(2+)-bound Aβ(42) aggregates into cytotoxic species in a copper chelation-independent manner

Increasing evidence indicates that abnormal Cu(2+) binding to Aβ peptides are responsible for the formation of soluble Aβ oligomers and ROS that play essential roles in AD pathogenesis. During studying the Cu(2+)-chelating treatment of Cu(2+)-bound Aβ(42) aggregates, we found that UV light exposure pronouncedly enhances cytotoxicity of the chelator-treated and -untreated Cu(2+)-bound Aβ(42) aggregates. This stimulated us to thoroughly investigate (1) either the chelation treatment or UV light exposure leads to the increased cytotoxicity of the aggregates, and (2) why the chelator-treated and -untreated Cu(2+)-bound Aβ(42) aggregates exhibit the increased cytotoxicity following UV light exposure if the latter is the case. The data indicated that the controlled UV exposure induced the dissociation of Cu(2+)-free and -bound Aβ(42) aggregates into SDS-stable soluble oligomers and the production of ROS including H(2)O(2) in an UV light intensity- and time-dependent, but Cu(2+) chelation-independent manner. Although we can’t fully understand the meaning of this finding at the current stage, the fact that the UV illuminated Aβ(42) aggregates can efficiently kill HeLa cells implies that the aggregates after UV light exposure could be used to decrease the viability of skin cancer cells through skin administration.