Nonlethal aluminum maltolate can reduce brain-derived neurotrophic factor-induced Arc expression through interrupting the ERK signaling in SH-SY5Y neuroblastoma cells

作者：Chen Tsan Ju^*; Cheng Hsiu Min; Wang Dean Chuan; Hung Hui Shan

来源：Toxicology Letters, 2011, 200(1-2): 67-76.

DOI：10.1016/j.toxlet.2010.10.016

• Aluminum
• Translation
• Arc
• BDNF

Although many studies have demonstrated that aluminum (Al) exposure impairs learning and memory, its underlying mechanism is still uncertain. Long-lasting forms of synaptic plasticity that underlie memory are dependent on new protein synthesis. In particular, activity-regulated cytoskeleton-associated protein (Arc) has a versatile role in synaptic plasticity, and its synthesis can be induced by brain-derived neurotrophic factor (BDNF). BDNF-induced Arc expression has been suggested to play a fundamental role in the stabilization of synaptic plasticity. In the present study, the pretreatment of Al(malt)(3) at nonlethal level (200 mu M, 24h) significantly reduced BDNF (10 ng/ml, 1 h)-induced Arc expression in SH-SY5Y human neuroblastoma cells. BDNF-induced activation of ERK but not PI3K signaling pathway was interfered with the Al(malt)(3) pretreatment, resulting in the subsequent reduction of BDNF-induced phosphorylation of 4EBP1, p70S6K, and eIF4E. Reduced phospho-4EBP1 and phospho-eIF4E hindered the initiation step of translation, which may lead to a reduction in BDNF-induced Arc expression. However, reduced phospho-p70S6K did not influence the phosphorylation of eEF2K and eEF2, indicating no significant effect on BDNF-enhanced translation elongation. Therefore, even at nonlethal level, Al(malt)(3) pretreatment reduced BDNF-induced Arc expression, which was caused by interrupting the ERK signaling pathway as well as the subsequent translation initiation.

• 出版日期2011-1-15