Intraneuronal aluminum potentiates iron-induced oxidative stress in cultured rat hippocampal neurons.
Aluminum can facilitate Fe-mediated oxidative injury, which may contribute to Al neurotoxicity. It has been reported that Al potentiates Fe-induced oxidative stress in cultured granule cells, suggesting a mechanism for Al facilitation of Fe-mediated oxidative injury. However, the relationship of intracellular Al concentration to Fe-induced oxidative stress has not been reported. In the present study, neuronal oxidative stress and survival were investigated. Embryo rat hippocampal neuron cultures were treated with Al2(SO4)3 and/or FeSO4. An ionophore, A23187, was utilized to facilitate cellular Al uptake. Intraneuronal Al concentration was ascertained by laser microprobe mass spectrometry (LMMS). Neuronal oxidative stress was measured by confocal laser scanning microscopy, using 2,7-dichlorofluorescin diacetate (DCFH-DA) as a probe. The study showed that neuronal Al uptake was facilitated by the ionophore and that an increase of intraneuronal Al concentration potentiated Fe-induced oxidative stress and neuronal death. The results indicate that Al potentiation of Fe-induced oxidative stress might contribute to Al facilitation of oxidative injury, and thus to Al neurotoxicity.
Xie
C X
CX
Graduate Center for Toxicology, University of Kentucky, Lexington, USA.
Mattson
M P
MP
Lovell
M A
MA
Yokel
R A
RA
D000535:Aluminum / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007476:Ionophores / Q000494:pharmacology; D007501:Iron / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007476:Ionophores; D009498:Neurotoxins; D000001:Calcimycin; D000535:Aluminum; D007501:Iron