Melatonin protects SH-SY5Y neuroblastoma cells from calyculin A-induced neurofilament impairment and neurotoxicity.
Hyperphosphorylation of cytoskeletal proteins seen in Alzheimer's disease is most probably the result of an imbalanced regulation in protein kinases and protein phosphatases (PP) in the affected neurons. Previous studies have revealed that PP-2A and PP-1 play important roles in the pathogenesis. Employing human neuroblastoma cells, we found that 10 nM calyculin A (CA), a selective inhibitor of PP-2A and PP-1, significantly increased phosphorylation and accumulation of neurofilament (NF) in the cells. Levels of NF-M (middle chain) and NF-L (light chain) mRNA decreased after CA treatment. Additionally, CA led to a decreased cell viability determined by MTT and crystal violet assay. Melatonin efficiently protects the cell from CA-induced alterations in NF hyperphosphorylation and accumulation, suppressed NF gene expression as well as decreased cell viability. It is concluded that inhibition of PP-2A/PP-1 by CA induces abnormalities in NF metabolism and cell survival, and melatonin efficiently arrests the lesions.
Li
Shu Peng
SP
Department of Pathophysiology, Institute of Neuroscience, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Deng
Yan Qiu
YQ
Wang
Xiao Chuan
XC
Wang
Yi Peng
YP
Wang
Jian-Zhi
JZ
D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity; D006801:Humans; D008387:Marine Toxins; D008550:Melatonin / Q000494:pharmacology*; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology*; D016900:Neurofilament Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000473:pathology; D010080:Oxazoles / Q000633:toxicity*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D010080:Oxazoles; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; D008550:Melatonin