title: The Effects of IGF-1 on Trk Expressing DRG Neurons with HIV-gp120- Induced Neurotoxicity.
abstract: BACKGROUND
  HIV envelope glycoprotein gp120 is the main protein that causes HIVassociated sensory neuropathy. However, the underlying mechanisms of gp120-induced neurotoxicity are still unclear. There are lack effective treatments for relieving HIV-related neuropathic symptoms caused by gp120-induced neurotoxicity.
  
  
  METHODS
  In the present study, tyrosine kinase receptor (Trk)A, TrkB, and TrkC expression in primary cultured dorsal root ganglion (DRG) neurons with gp120-induced neurotoxicity was investigated. The effects of IGF-1 on distinct Trk-positive DRG neurons with gp120-induced neurotoxicity were also determined.
  
  
  RESULTS
  The results showed that gp120 not only dose-dependently induced DRG neuronal apoptosis and inhibited neuronal survival and neurite outgrowth, but also decreased distinct Trk expression levels. IGF-1 rescued DRG neurons from apoptosis and improved neuronal survival of gp120 neurotoxic DRG neurons in vitro. IGF-1 also improved TrkA and TrkB, but not TrkC, expression in gp120 neurotoxic conditions. The effects of IGF-1 could be blocked by preincubation with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002.
  
  
  CONCLUSIONS
  These results suggested that gp120 may have a wide range of neurotoxicity on different subpopulations of DRG neurons, while IGF-1 might only relieve some subpopulations of DRG neurons with gp120-induced neurotoxicity. These data provide novel information of mechanisms of gp120 neurotoxicity on primary sensory neurons and the potential therapeutic effects of IGF-1 on gp120-induced neurotoxicity.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Heng
authors.initials: H
authors.lastname: Chi
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Bi
authors.forename: Lijun
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Rheumatology, Shandong University Qilu Hospital, 107 Wenhua Xi Road, Jinan, Shandong Province 250012, China. huaxiangliu@hotmail.com.
authors.forename: Huaxiang
authors.initials: H
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000503:physiopathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
chemical_list: D015699:HIV Envelope Protein gp120; D007334:Insulin-Like Growth Factor I; D020794:Receptor Protein-Tyrosine Kinases