Exacerbation of copper toxicity in primary neuronal cultures depleted of cellular glutathione.

摘要: Perturbations to glutathione (GSH) metabolism may play an important role in neurodegenerative disorders such as Alzheimer's, Parkinson's, and prion diseases. A primary function of GSH is prevent the toxic interaction between free radicals reactive transition metals copper (Cu). Due potential Cu neurodegeneration, we examined effect depletion on toxicity murine neuronal cultures. Depletion cellular with L-buthionine-[S,R]-sulfoximine resulted a dramatic potentiation neurons without iron (Fe) toxicity. Similarly, inhibition reductase (GR) activity 1,3-bis(2-chloroethyl)-1-nitrosurea also increased neurons. To determine if Alzheimer's amyloid-beta (Abeta) peptide can affect resistance metal toxicity, exposed cultures nontoxic concentrations Abeta25-35 presence or absence Fe. pretreatment was found deplete increase GR activity, confirming ability Abeta perturb homeostasis. potently but had no Fe These studies demonstrate for homeostasis selective protection against finding widespread implications disorders.