Regulation of Amyloid Beta Interactions with Humanin and Acetylcholinesterase in Lung Cancer Cell Media

Abstract

Humanin (HN) is known to bind amyloid beta (Aβ) inducing cytoprotective effects while binding of acetylcholinesterase (AChE) to Aβ increases its aggregation and cytotoxicity. Here, we set out to shed light on factors that modulate the interactions of Aβ with HN and AChE. We found that binding of either HN or AChE to Aβ is not affected by heparan sulfate, while ATP, thought to reduce misfolding of Aβ, weakened interactions between AChE and Aβ but strengthened those between Aβ and HN. Using media from either A549 or H1299 lung cancer cells, more HN was bound with Aβ upon addition of ATP, while levels of AChE in a complex with Aβ were decreased by ATP addition to A549 cell media. Immunodepletion of HN from the media of A549 and H1299 cells increased the relative abundance of oligomer versus total Aβ and correlated with diminished cell viability and increased apoptosis. Exogenously added ATP, however, did not affect viability of cells treated with AChE-immunodepleted media and there was no apparent protection against the cytotoxicity resulting from immunodepletion of HN. Moreover, exogenously added ATP had no effect on the relative abundance of oligomer versus total Aβ in either cell line.