title: Gambogic amide selectively upregulates TrkA expression and triggers its activation.
abstract: BACKGROUND
  Gambogic amide is the first identified small molecular agonist for TrkA receptor. It mimics NGF functions by selectively activating TrkA receptor and preventing neuron death. However, its function different from that of NGF remains unknown.
  
  
  METHODS
  In the current study, we detect the effect of gambogic amide on TrkA expression using TrkA-expressing cell lines in vitro and hippocampi from mice treated with gambogic amide.
  
  
  RESULTS
  We have confirmed that gambogic amide displays robust neurotrophic activities in provoking neurite outgrowth in vitro. However, gambiogic amide displays a different kinetics from NGF in activating TrkA signals. NGF swiftly provokes TrkA activation and quickly induces TrkA degradation, while gambogic amid selectively upregulates TrkA protein and mRNA levels in a time-dependent manner. Administration of this compound in mice also activates TrkA receptor in hippocampus and promotes TrkA transcription and expression.
  
  
  CONCLUSIONS
  This study provides a novel mechanism of how gambogic amide regulates TrkA receptor, other than mimicking NGF in triggering TrkA activation.
authors.affiliation: Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Shen
authors.affiliation: Center for Osteonecrosis and Joint Preserving and Reconstruction, Department of Orthopedics, China-Japan Friendship Hospital, Beijing, China. Electronic address: qingshengy@gmail.com.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D020917:Receptor, trkA / Q000819:agonists* / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D013379:Substrate Specificity; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D009414:Nerve Growth Factors; D044004:Xanthones; C052659:gambogic acid; D020932:Nerve Growth Factor; D020917:Receptor, trkA; C545053:gambogic amide
keywords: Gambogic amide; Nerve growth factor; Neurotrophic effect; Transcription; TrkA agonist