Nonlethal aluminum maltolate can reduce brain-derived neurotrophic factor-induced Arc expression through interrupting the ERK signaling in SH-SY5Y neuroblastoma cells.
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 μM, 24 h) significantly reduced BDNF (10 ng/ml, 1h)-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.
Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. tsanju@kmu.edu.tw
Tsan-Ju
TJ
Chen
Hsiu-Min
HM
Cheng
Dean-Chuan
DC
Wang
Hui-Shan
HS
Hung
D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009447:Neuroblastoma / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D010766:Phosphorylation; D011753:Pyrones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009942:Organometallic Compounds; D011753:Pyrones; C092069:activity regulated cytoskeletal-associated protein; C067527:aluminum maltolate; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases