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Cadmium-Induced Toxicity in Rat Primary Mid-brain Neuroglia Cultures: Role of Oxidative Stress from Microglia

This study examined the role of oxidative stress in neurotoxic effects of cadmium chloride (Cd) in rat primary mid-brain neuron-glia cultures. Cd accumulated in neuron-glia cultures and produced cytotoxicity in a dose-dependent manner, with IC50 of 2.5μM 24 h after exposure. 3H-dopamine uptake into...

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Published in:Toxicological sciences 2007-08, Vol.98 (2), p.488-494
Main Authors: Yang, Zhengqin, Yang, Sufen, Qian, Steven Y., Hong, Jau-Shyong, Kadiiska, Maria B., Tennant, Raymond W., Waalkes, Michael P., Liu, Jie
Format: Article
Language:English
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Summary:This study examined the role of oxidative stress in neurotoxic effects of cadmium chloride (Cd) in rat primary mid-brain neuron-glia cultures. Cd accumulated in neuron-glia cultures and produced cytotoxicity in a dose-dependent manner, with IC50 of 2.5μM 24 h after exposure. 3H-dopamine uptake into neuron-glia cultures was decreased 7 days after Cd exposure, with IC50 of 0.9μM, indicative of the sensitivity of dopaminergic neurons to Cd toxicity. To investigate the role of microglia in Cd-induced toxicity to neurons, microglia-enriched cultures were prepared. Cd significantly increased intracellular reactive oxygen species production in microglia-enriched cultures, as evidenced by threefold increases in 2′,7′-dichlorofluorescein signals. Using 5,5-dimethyl-1-pyrroline N-oxide as a spin-trapping agent, Cd increased electron spin resonance signals by 3.5-fold in microglia-enriched cultures. Cd-induced oxidative stress to microglia-enriched cultures was further evidenced by activation of redox-sensitive transcription factor nuclear factor kappa B and activator protein-1 (AP-1), and the increased expression of oxidative stress-related genes, such as metallothionein, heme oxygenase-1, glutathione S-transferase pi, and metal transport protein-1, as determined by gel-shift assays and real-time reverse transcription–PCR, respectively, in microglia-enriched cultures. In conclusion, Cd is toxic to neuron-glia cultures, and the oxidative stress from microglia may play important roles in Cd-induced damage to dopaminergic neurons.
ISSN:1096-6080
1096-0929
DOI:10.1093/toxsci/kfm106