title: Nitric oxide mediates TNF-α-induced apoptosis in the auditory cell line.
abstract: OBJECTIVE
  Tumor necrosis factor-alpha (TNF-α) is released in a variety of pathological states in the inner ear. Inducible nitric oxide synthase (iNOS) can be induced by cytokines and other inflammatory factors, and is generally thought to be associated with inflammation and other pathological processes in the cochlea. The purpose of the present study was to reveal that TNF-α could induce apoptosis in the auditory cell line and to investigate the role of nitric oxide (NO) in TNF-α-induced auditory cell death.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  UB-OC1 cells and zebrafish were exposed to TNF-α. Flow cytometry, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assay, assay of mitochondrial membrane potential (MMP), and electron microscopy were used to show that TNF-α could induce apoptosis. Western blot was used to measure iNOS expression and mitogen-activated protein kinase pathway.
  
  
  RESULTS
  Flow cytometric analysis, TUNEL assay, MMP, and electron microscopy all demonstrated that TNF-α could induce apoptosis in UB-OC1 cells. TNF-α significantly increased NO generation and iNOS expression. Pretreatment with iNOS blocker NG-methyl-L-arginine (NMA) attenuated TNF-α-induced cell death and caspase-3 activation. Also, TNF-α treatment increased p-p38 and p-ERK, and pretreatment of NMA reduced this increased expression of p-p38 and p-ERK.
  
  
  CONCLUSIONS
  TNF-α can induce apoptosis in the auditory cell line, and NO production in response to TNF-α is essential for apoptosis.
authors: Department of OtolaryngologyAjou University School of Medicine, Suwon, South Korea.
authors: Hun Yi
authors: HY
authors: Park
authors: Mi Hye
authors: MH
authors: Lee
authors: Sung Un
authors: SU
authors: Kang
authors: Hye Sook
authors: HS
authors: Hwang
authors: Keehyun
authors: K
authors: Park
authors: Yun-Hoon
authors: YH
authors: Choung
authors: Chul-Ho
authors: CH
authors: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide