Huperzine A protects SHSY5Y neuroblastoma cells against oxidative stress damage via nerve growth factor production

Eur J Pharmacol. 2005 Sep 5;519(1-2):9-15. doi: 10.1016/j.ejphar.2005.06.026.


Our previous study demonstrated that huperzine A, a selective acetylcholinesterase inhibitor, stimulates the synthesis of nerve growth factor (NGF) in cultured rat cortical astrocytes. The present studies are designed to examine if huperzine A exerts its neuroprotective activity against oxidative stress damage through increasing the synthesis of NGF in SHSY5Y neuroblastoma cells. Transient exposure of the cells to 200 microM H2O2 triggered a significant reduction of cell viability and decreased the mRNA and protein levels of NGF, neurotrophin receptor P75 (P75NTR) receptor and tyrosine kinase A (TrkA) receptor. Incubation of cells with 10 microM huperzine A prior to H2O2 exposure significantly elevated their survival and restored the mRNA and protein levels of NGF, P75NTR receptor and TrkA receptor. These neuroprotective effects of huperzine A on H2O2-induced cytotoxicity were blocked by the TrkA receptor phosphorylation inhibitor K252alpha, and were antagonized by the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) inhibitor, PD98059. The present results indicate that the cytoprotective effect of huperzine A is mediated at least partly by up-regulated NGF and NGF receptors. The results also show that the MAP/ERK kinase signal pathway is crucial for huperzine A to protect against H2O2-induced damage in SHSY5Y cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids
  • Androstadienes / pharmacology
  • Blotting, Western
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Carbazoles / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Immunohistochemistry
  • Indole Alkaloids
  • Nerve Growth Factor / genetics*
  • Nerve Growth Factor / metabolism
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Neuroprotective Agents / pharmacology
  • Oxidants / pharmacology
  • Oxidative Stress / drug effects*
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Nerve Growth Factor
  • Receptor, trkA / genetics
  • Receptor, trkA / metabolism
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sesquiterpenes / pharmacology*
  • Wortmannin


  • Alkaloids
  • Androstadienes
  • Carbazoles
  • Enzyme Inhibitors
  • Flavonoids
  • Indole Alkaloids
  • Neuroprotective Agents
  • Oxidants
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor
  • Sesquiterpenes
  • huperzine A
  • Nerve Growth Factor
  • staurosporine aglycone
  • Hydrogen Peroxide
  • Receptor, trkA
  • Calcium-Calmodulin-Dependent Protein Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Wortmannin