Hydrogen peroxide modifies both activity and isoforms of acetylcholinesterase in human neuroblastoma SH-SY5Y cells.

The involvement of cholinergic system and the reactive oxygen species (ROS) in the pathogenesis of some degenerative diseases has been widely reported; however, the specific impact of hydrogen peroxide (H(2)O(2)) on the acetylcholinesterase (AChE) activity as well as AChE isoform levels has not been clearly established. Hence, the purpose of present study is to clarify whether H(2)O(2) alters these parameters. Human neuroblastoma SH-SY5Y cells were treated with H(2)O(2) (1-1000µM) for 24h and AChE activity and AChE and cytochrome c levels were evaluated. AChE activity was strongly increased from 1µM to 1000µM of H(2)O(2.) The results of the kinetic study showed that H(2)O(2) affected Vmax but not Km; and also that H(2)O(2) changed the sigmoid kinetic observed in control samples to hyperbolic kinetic. Thus, results suggest that H(2)O(2) acts as an allosteric activators. In addition, H(2)O(2), (100-1000µM) reduced the total AChE content and modified its isoform profile (mainly 50-, 70-, and 132-kDa)·H(2)O(2) from 100µM to 1000µM induced cytochrome c release confirming cell death by apoptosis. All these results together suggest: a) the involvement of oxidative stress in the imbalance of AChE; and b) treatment with antioxidant agents may be a suitable strategy to protect cholinergic system alterations promoted by oxidative stress.