title: Subtoxic levels of hydrogen peroxide induce brain-derived neurotrophic factor expression to protect PC12 cells.
abstract: BACKGROUND
  Oxidative stress is one of the mechanisms underlying pathogenesis in neurodegenerative diseases such as Alzheimer's disease. Generally, oxidative stress represents cell toxicity; however, we recently found that oxidative stress promotes the expression of growth factor progranulin (PGRN) in HT22 murine hippocampus cells, thereby protecting the HT22 cells. In this study, we attempted to clarify whether a similar system exists in the other neuronal cell model, rat pheochromocytoma (PC12) cells.
  
  
  RESULTS
  After confirming that high concentrations of hydrogen peroxide (H2O2; 100-250 μM) initiate PC12 cell death, we analyzed growth factor expressional changes after H2O2 treatment. We found, intriguingly, that gene expression of brain-derived neurotrophic factor (BDNF), but not PGRN was significantly induced by H2O2. Although little expression of the high affinity BDNF receptor tropomyosin-related kinase TrkB was observed in PC12 cells, expression of low affinity neurotrophin receptor, p75NTR, was clearly observed. This BDNF signaling appeared to contribute to PC12 cell protection, since PC12 cell death was significantly attenuated by BDNF treatment.
  
  
  CONCLUSIONS
  Based on our results, we conclude that the induction of BDNF by subtoxic levels of H2O2 and its signaling may have roles in PC12 cell protection.
authors.forename: Yurina
authors.initials: Y
authors.lastname: Ogura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sato
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kawashima
authors.forename: Nanako
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Sei
authors.initials: S
authors.lastname: Imura
authors.forename: Kotaro
authors.initials: K
authors.lastname: Fujino
authors.forename: Hideo
authors.initials: H
authors.lastname: Kawaguchi
authors.affiliation: Department of Life Sciences, Graduate School of Life Sciences, Toyo University, 1-1-1 Izumino, Itakura-machi, Oura-gun, Gunma 374-0193, Japan. nedachi@toyo.jp.
authors.forename: Taku
authors.initials: T
authors.lastname: Nedachi
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000819:agonists / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D018384:Oxidative Stress; D016716:PC12 Cells; D000077153:Progranulins; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C084619:Grn protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D000077153:Progranulins; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C068313:Ngfr protein, rat; D006861:Hydrogen Peroxide; D020813:Receptor, trkB