Lanthanum induced primary neuronal apoptosis through mitochondrial dysfunction modulated by Ca²⁺ and Bcl-2 family.
Jie Wu, Jinghua Yang, Qiufang Liu, Shengwen Wu, Honglin Ma, Yuan Cai
Index: Biol. Trace Elem. Res. 152(1) , 125-34, (2013)
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Abstract
As a representative element of lanthanide, lanthanum has been widely used in various fields and eventually entered environment and accumulated in human body. Epidemiological and experimental evidences indicated that lanthanum has neurotoxicity; however, the detailed mechanism is still elusive. Here, we chose primary cerebral cortical neurons as model in vitro to investigate the mechanism underlying the toxic effects of lanthanum chloride (LaCl3). This study revealed the following findings: (1) LaCl3 treatment (0.01, 0.1, and 1.0 mM for 24 h) reduced the viability of cortical neurons and elevated apoptotic rate significantly in a dose-dependent manner. (2) LaCl3 triggered mitochondrial apoptotic pathway in cortical neurons, characterized with collapsed mitochondrial membrane potential, release of cytochrome c into cytosol, and increasing expression of activated caspase-3. (3) LaCl3 elevated intracellular Ca(2+) concentration, promoted reactive oxygen species generation, and upregulated pro-apoptotic Bax, whereas it downregulated anti-apoptotic Bcl-2 expression and consequently altered Bax/Bcl-2 ratio, which ultimately lead to neuronal mitochondrial apoptosis. Our results demonstrated that toxicity of lanthanum in cortical neurons perhaps partly attributed to enhanced mitochondrial apoptosis due to mitochondrial dysfunction modulated by Ca(2+) and Bcl-2 family.
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