TY - JOUR
T1 - Mercury induces cell cytotoxicity and oxidative stress and increases β- amyloid secretion and tau phosphorylation in SHSY5Y neuroblastoma cells
AU - Olivieri, G.
AU - Brack, Ch
AU - Müller-Spahn, F.
AU - Stähelin, H. B.
AU - Herrmann, M.
AU - Renard, P.
AU - Brockhaus, M.
AU - Hock, C.
PY - 2000
Y1 - 2000
N2 - Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer's disease (AD) patients. To explore potential pathophysiological mechanisms we used an in vitro model system (SHSY5Y neuroblastoma cells) and investigated the effects of inorganic mercury (HgCl2) on oxidative stress, cell cytotoxicity; β-amyloid production, and tau phosphorylation. We demonstrated that exposure of cells to 50 μg/L (180 nM) HgCl2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels (n = 13, p < 0.001). Preincubation of cells for 30 min with I μM melatonin or premixing melatonin and HgCl2 appeared to protect cells from the mercury-induced GSH loss. Similarly, 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that 50 μg/L HgCl2 for 24 h produced a 50% inhibition of MTT reduction (n = 9, p < 0.001). Again, melatonin preincubation protected cells from the deleterious effects of mercury, resulting in MTT reduction equaling control levels. The release of β-amyloid peptide (Aβ) 1-40 and 1- 42 into cell culture supernatants after exposure to HgCl2 was shown to be different: Aβ 1-40 showed maximal (15.3 ng/ml) release after 4 h, whereas Aβ 1-42 showed maximal (9,3 ng/ml) release after 6 h of exposure to mercury compared with untreated controls (n = 9, p < 0.001). Preincubation of cells with melatonin resulted in an attenuation of Aβ 1-40 and Aβ 1-42 release. Tau phosphorylation was significantly increased in the presence of mercury (n = 9, ρ < 0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD.
AB - Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer's disease (AD) patients. To explore potential pathophysiological mechanisms we used an in vitro model system (SHSY5Y neuroblastoma cells) and investigated the effects of inorganic mercury (HgCl2) on oxidative stress, cell cytotoxicity; β-amyloid production, and tau phosphorylation. We demonstrated that exposure of cells to 50 μg/L (180 nM) HgCl2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels (n = 13, p < 0.001). Preincubation of cells for 30 min with I μM melatonin or premixing melatonin and HgCl2 appeared to protect cells from the mercury-induced GSH loss. Similarly, 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that 50 μg/L HgCl2 for 24 h produced a 50% inhibition of MTT reduction (n = 9, p < 0.001). Again, melatonin preincubation protected cells from the deleterious effects of mercury, resulting in MTT reduction equaling control levels. The release of β-amyloid peptide (Aβ) 1-40 and 1- 42 into cell culture supernatants after exposure to HgCl2 was shown to be different: Aβ 1-40 showed maximal (15.3 ng/ml) release after 4 h, whereas Aβ 1-42 showed maximal (9,3 ng/ml) release after 6 h of exposure to mercury compared with untreated controls (n = 9, p < 0.001). Preincubation of cells with melatonin resulted in an attenuation of Aβ 1-40 and Aβ 1-42 release. Tau phosphorylation was significantly increased in the presence of mercury (n = 9, ρ < 0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD.
KW - β-Amyloid
KW - Melatonin
KW - Mercury
KW - Oxidative stress
KW - SHSY5Y neuroblastoma cells
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=0033957486&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.2000.0740231.x
DO - 10.1046/j.1471-4159.2000.0740231.x
M3 - Article
C2 - 10617124
SN - 0022-3042
VL - 74
SP - 231
EP - 236
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 1
ER -