title: Insulin-like growth factor binding protein (IGFBP)-mediated hair cell survival on the mouse utricle exposed to neomycin: the roles of IGFBP-4 and IGFBP-5.
abstract: CONCLUSIONS
  This study suggests for the first time that 1) IGF-I, IGFBP-4, and -5 alone and IGF-I+IGFBP-5 mixture stimulated hair cell survival and prevented neomycin-induced hair cell loss in the sensory epithelial culture of mouse utricles, 2) When administered together, IGFBP-4 diminished the effect of IGF-I, 3) In P3-5 mice utricle, IGF-I, IGFBP-4, and IGFBP-5 are expressed in the cytoplasm of hair cells. And Insulin/IGF-I Receptor is expressed in the nucleus of hair cells.
  
  
  OBJECTIVE
  Several growth factors have been demonstrated to protect auditory sensory cells in vitro and in vivo from aminoglycoside toxicity. IGF-I is one of the most well-known mitogenic and protective substance working in the inner ear. However, there are no reports available regarding the function of IGFBPs in the inner ear. In the present study, the effects of IGFBP-4 and -5 on hair cell survival were investigated in mouse utriclular organ cultures.
  
  
  METHODS
  The amount of cellular damage and cell viability in vestibular organs were assessed by counting hair cells stained with a rhodamine-phalloidin probe. The expressions of IGFBP-4, IGFBP-5, IGF-IR, and IGF-I were localized by immunohistochemistry.
  
  
  RESULTS
  When treated with IGF-I, IGFBP-4, or IGFBP-5 for 24 h, explant culture showed hair cell survival rates of 136+/-18%, 140+/-15%, and 133+/-6%, respectively, compared to controls. Neomycin (1 mM) induced hair cell loss resulted in 45+/-17% of hair cell survival. However, pre-treatment of IGF-I, IGFBP-4, or -5 before neomycin insult showed survival rates of 113+/-14%, 98+/-8%, and 73+/-24%, respectively. Similar to IGF-I, IGFBP-4 and IGFBP-5 were significantly protective. IGFBP-4 and -5 immunoreactivities were observed in the cytoplasm of normal explanted vestibular hair cells as well as in the P3 mouse utricular hair cells in vivo.
authors: Department of Otorhinolaryngology, Seoul National University, Seoul, Korea.
authors: Ji Yeong
authors: JY
authors: Park
authors: Yong Ho
authors: YH
authors: Park
authors: Dong Hoon
authors: DH
authors: Shin
authors: Seung Ha
authors: SH
authors: Oh
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism / Q000494:pharmacology*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D023421:Models, Animal; D009355:Neomycin / Q000633:toxicity*
chemical_list: D000900:Anti-Bacterial Agents; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D007334:Insulin-Like Growth Factor I; D009355:Neomycin