PMID- 22815072
OWN - NLM
STAT- MEDLINE
DCOM- 20121205
LR  - 20131121
IS  - 1531-4995 (Electronic)
IS  - 0023-852X (Linking)
VI  - 122
IP  - 10
DP  - 2012 Oct
TI  - Nitric oxide mediates TNF-alpha-induced apoptosis in the auditory cell line.
PG  - 2256-64
LID - 10.1002/lary.23444 [doi]
AB  - OBJECTIVES/HYPOTHESIS: Tumor necrosis factor-alpha (TNF-alpha) 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-alpha could induce apoptosis in the auditory cell line and to investigate the 
      role of nitric oxide (NO) in TNF-alpha-induced auditory cell death. STUDY DESIGN: 
      Experimental study. METHODS: UB-OC1 cells and zebrafish were exposed to TNF-alpha. 
      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-alpha 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-alpha could induce apoptosis in UB-OC1 cells. 
      TNF-alpha significantly increased NO generation and iNOS expression. Pretreatment 
      with iNOS blocker NG-methyl-L-arginine (NMA) attenuated TNF-alpha-induced cell death 
      and caspase-3 activation. Also, TNF-alpha treatment increased p-p38 and p-ERK, and 
      pretreatment of NMA reduced this increased expression of p-p38 and p-ERK. 
      CONCLUSIONS: TNF-alpha can induce apoptosis in the auditory cell line, and NO 
      production in response to TNF-alpha is essential for apoptosis.
CI  - Copyright (c) 2012 The American Laryngological, Rhinological, and Otological 
      Society, Inc.
FAU - Park, Hun Yi
AU  - Park HY
AD  - Department of OtolaryngologyAjou University School of Medicine, Suwon, South 
      Korea.
FAU - Lee, Mi Hye
AU  - Lee MH
FAU - Kang, Sung Un
AU  - Kang SU
FAU - Hwang, Hye Sook
AU  - Hwang HS
FAU - Park, Keehyun
AU  - Park K
FAU - Choung, Yun-Hoon
AU  - Choung YH
FAU - Kim, Chul-Ho
AU  - Kim CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120719
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Cell Line
MH  - Cell Survival
MH  - Hair Cells, Auditory, Inner/cytology/*metabolism/ultrastructure
MH  - MAP Kinase Signaling System/physiology
MH  - Mice
MH  - Mitochondria/metabolism/ultrastructure
MH  - Nitric Oxide/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Zebrafish
EDAT- 2012/07/21 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/07/21 06:00
PHST- 2011/11/02 00:00 [received]
PHST- 2012/03/30 00:00 [revised]
PHST- 2012/04/26 00:00 [accepted]
PHST- 2012/07/21 06:00 [entrez]
PHST- 2012/07/21 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - 10.1002/lary.23444 [doi]
PST - ppublish
SO  - Laryngoscope. 2012 Oct;122(10):2256-64. doi: 10.1002/lary.23444. Epub 2012 Jul 
      19.