Premium
N ‐Acetyl‐ l ‐cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on β‐amyloid secretion and tau phosphorylation
Author(s) -
Olivieri G.,
Baysang G.,
Meier F.,
MüllerSpahn F.,
Stähelin H. B.,
Brockhaus M.,
Brack CH.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00090.x
Subject(s) - oxidative stress , cytotoxicity , glutathione , secretion , intracellular , biochemistry , chemistry , oxidative phosphorylation , phosphorylation , antioxidant , cell culture , microbiology and biotechnology , biology , enzyme , in vitro , genetics
Redox changes within neurones are increasingly being implicated as an important causative agent in brain ageing and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). Cells have developed a number of defensive mechanisms to maintain intracellular redox homeostasis, including the glutathione (GSH) system and antioxidant enzymes. Here we examine the effects of N ‐acetyl‐ l ‐cysteine (NAC) on β‐amyloid (Aβ) secretion and tau phosphorylation in SHSY5Y neuroblastoma cells after exposure to oxidative stress inducing/cytotoxic compounds (H 2 O 2 , UV light and toxic Aβ peptides). Aβ and tau protein are hallmark molecules in the pathology of AD while the stress factors are implicated in the aetiology of AD. The results show that H 2 O 2 , UV light, Aβ1–42 and toxic Aβ25–35, but not the inactive Aβ35–25, produce a significant induction of oxidative stress and cell cytotoxicity. The effects are reversed when cells are pre‐treated with 30 m m NAC. Cells exposed to H 2 O 2 , UV light and Aβ25–35, but not Aβ35–25, secrete significantly higher amounts of Aβ1–40 and Aβ1–42 into the culture medium. NAC pre‐treatment increased the release of Aβ1–40 compared with controls and potentiated the release of both Aβ1–40 and Aβ1–42 in Aβ25–35‐treated cells. Tau phosphorylation was markedly reduced by H 2 O 2 and UV light but increased by Aβ25–35. NAC strongly lowered phospho‐tau levels in the presence or absence of stress treatment.