PMID- 17079781
OWN - NLM
STAT- MEDLINE
DCOM- 20070517
LR  - 20181113
IS  - 1044-1549 (Print)
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Linking)
VI  - 36
IP  - 4
DP  - 2007 Apr
TI  - Nonphagocytic oxidase 1 causes death in lung epithelial cells via a TNF-RI-JNK 
      signaling axis.
PG  - 473-9
AB  - Airway epithelial cells are simultaneously exposed to and produce cytokines and 
      reactive oxygen species (ROS) in inflammatory settings. The signaling events and 
      the physiologic outcomes of exposure to these inflammatory mediators remain to be 
      elucidated. Previously we demonstrated that in cultured mouse lung epithelial 
      cells exposed to bolus administration of H(2)O(2), TNF-alpha-induced NF-kappaB 
      activity was inhibited, whereas c-Jun-N-terminal kinase (JNK) activation was 
      enhanced via a mechanism involving TNF receptor-1 (TNF-RI). In this study we used 
      the nonphagocytic NADPH oxidase (Nox1) to study the effects of endogenously 
      produced ROS on a line of mouse alveolar type II epithelial cells. Nox1 
      expression and activation inhibited TNF-alpha-induced inhibitor of kappaB kinase 
      (IKK), and NF-kappaB while promoting JNK activation and cell death. Nox1-induced 
      JNK activation and cell death were attenuated through expression of a 
      dominant-negative TNF-RI construct, implicating a role for TNF-RI in Nox1 
      signaling. Furthermore, Nox1 used the TNF-RI adaptor protein 
      TNF-receptor-associated factor-2 (TRAF2), and the redox-regulated JNK MAP3K, 
      apoptosis signal kinase-1 (ASK1), to activate JNK. In addition, ASK1 siRNA 
      attenuated both Nox1-induced JNK activity and cell death. Collectively, these 
      studies suggest a mechanism by which ROS produced in lung epithelial cells 
      activate JNK and cause cell death using TNF-RI and the TRAF2-ASK1 signaling axis.
FAU - Pantano, Cristen
AU  - Pantano C
AD  - Department of Pathology, University of Vermont College of Medicine, 89 Beaumont 
      Avenue, HSRF 216A, Burlington, VT 05405, USA.
FAU - Anathy, Vikas
AU  - Anathy V
FAU - Ranjan, Priya
AU  - Ranjan P
FAU - Heintz, Nicholas H
AU  - Heintz NH
FAU - Janssen-Heininger, Yvonne M W
AU  - Janssen-Heininger YM
LA  - eng
GR  - P01 HL67004/HL/NHLBI NIH HHS/United States
GR  - P20 RL15557/PHS HHS/United States
GR  - R01 HL60014/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20061101
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.6.- (NADH, NADPH Oxidoreductases)
RN  - EC 1.6.3.- (NADPH Oxidase 1)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.- (NOX1 protein, human)
RN  - EC 1.6.3.- (NOX1 protein, mouse)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
SB  - IM
MH  - Animals
MH  - Cell Death
MH  - Cell Line
MH  - Lung/cytology/*enzymology
MH  - MAP Kinase Kinase 4/*metabolism
MH  - Mice
MH  - NADH, NADPH Oxidoreductases/*metabolism/physiology
MH  - NADPH Oxidase 1
MH  - NADPH Oxidases/*metabolism/physiology
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I/*metabolism
MH  - Respiratory Mucosa/cytology/*enzymology
MH  - Signal Transduction
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/pharmacology
PMC - PMC1899325
EDAT- 2006/11/03 09:00
MHDA- 2007/05/18 09:00
PMCR- 2008/04/01
CRDT- 2006/11/03 09:00
PHST- 2006/11/03 09:00 [pubmed]
PHST- 2007/05/18 09:00 [medline]
PHST- 2006/11/03 09:00 [entrez]
PHST- 2008/04/01 00:00 [pmc-release]
AID - 2006-0109OC [pii]
AID - ajrcmb364473 [pii]
AID - 10.1165/rcmb.2006-0109OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2007 Apr;36(4):473-9. doi: 10.1165/rcmb.2006-0109OC. 
      Epub 2006 Nov 1.