Ultraviolet light triggers the conversion of Cu2+-bound A?42 aggregates into cytotoxic species in a copper chelation-independent manner.

ABSTRACT: Increasing evidence indicates that abnormal Cu2+ binding to A? peptides are responsible for the formation of soluble A? oligomers and ROS that play essential roles in AD pathogenesis. During studying the Cu2+-chelating treatment of Cu2+-bound A?42 aggregates, we found that UV light exposure pronouncedly enhances cytotoxicity of the chelator-treated and -untreated Cu2+-bound A?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 Cu2+-bound A?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 Cu2+-free and -bound A?42 aggregates into SDS-stable soluble oligomers and the production of ROS including H2O2 in an UV light intensity- and time-dependent, but Cu2+ chelation-independent manner. Although we can't fully understand the meaning of this finding at the current stage, the fact that the UV illuminated A?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.

SUBMITTER: Dong X 

PROVIDER: S-EPMC4563556 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature