PMID- 22425780
OWN - NLM
STAT- MEDLINE
DCOM- 20121213
LR  - 20211021
IS  - 1089-8611 (Electronic)
IS  - 1089-8603 (Print)
IS  - 1089-8603 (Linking)
VI  - 26
IP  - 4
DP  - 2012 May 15
TI  - Normoxic cyclic GMP-independent oxidative signaling by nitrite enhances airway 
      epithelial cell proliferation and wound healing.
PG  - 203-10
LID - 10.1016/j.niox.2012.03.002 [doi]
AB  - The airway epithelium provides important barrier and host defense functions. 
      Recent studies reveal that nitrite is an endocrine reservoir of nitric oxide (NO) 
      bioactivity that is converted to NO by enzymatic reductases along the 
      physiological oxygen gradient. Nitrite signaling has been described as NO 
      dependent activation mediated by reactions with deoxygenated redox active 
      hemoproteins, such as hemoglobin, myoglobin, neuroglobin, xanthine oxidoreductase 
      (XO) and NO synthase at low pH and oxygen tension. However, nitrite can also be 
      readily oxidized to nitrogen dioxide (NO(2).) via heme peroxidase reactions, 
      suggesting the existence of alternative oxidative signaling pathways for nitrite 
      under normoxic conditions. In the present study, we examined normoxic signaling 
      effects of sodium nitrite on airway epithelial cell wound healing. In an in vitro 
      scratch injury model under normoxia, we exposed cultured monolayers of human 
      airway epithelial cells to various concentrations of sodium nitrite and compared 
      responses to NO donor. We found sodium nitrite potently enhanced airway 
      epithelium wound healing at physiological concentrations (from 1 muM). The effect 
      of nitrite was blocked by the NO and NO(2). scavenger 
      2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO). 
      Interestingly, nitrite treatment did not increase cyclic guanosine monophosphate 
      (cGMP) levels under these normoxic conditions, even in the presence of a 
      phosphodiesterase 5 inhibitor, suggesting cGMP independent signaling. Consistent 
      with an oxidative signaling pathway requiring hydrogen peroxide 
      (H(2)O(2))/heme-peroxidase/NO(2). signaling, the effects of nitrite were 
      potentiated by superoxide dismutase (SOD) and low concentration H(2)O(2), whereas 
      inhibited completely by catalase, followed by downstream 
      extracellular-signal-regulated kinase (ERK) 1/2 activation. Our data represent 
      the first description of normoxic nitrite signaling on lung epithelial cell 
      proliferation and wound healing and suggest novel oxidative signaling pathways 
      involving nitrite-H(2)O(2) reactions, possibly via the intermediary, NO(2)..
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Wang, Ling
AU  - Wang L
AD  - Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
FAU - Frizzell, Sheila A
AU  - Frizzell SA
FAU - Zhao, Xuejun
AU  - Zhao X
FAU - Gladwin, Mark T
AU  - Gladwin MT
LA  - eng
GR  - P01 HL103455/HL/NHLBI NIH HHS/United States
GR  - RC1 DK085852/DK/NIDDK NIH HHS/United States
GR  - R01 HL098032/HL/NHLBI NIH HHS/United States
GR  - R01HL098032/HL/NHLBI NIH HHS/United States
GR  - R01 HL096973/HL/NHLBI NIH HHS/United States
GR  - R01HL096973/HL/NHLBI NIH HHS/United States
GR  - P01HL103455/HL/NHLBI NIH HHS/United States
GR  - RC1DK085852/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120308
PL  - United States
TA  - Nitric Oxide
JT  - Nitric oxide : biology and chemistry
JID - 9709307
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Reactive Oxygen Species)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - M0KG633D4F (Sodium Nitrite)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Analysis of Variance
MH  - Cell Line, Transformed
MH  - Cell Proliferation/*drug effects
MH  - Epithelial Cells/drug effects/metabolism
MH  - Free Radical Scavengers
MH  - Humans
MH  - Hydrogen Peroxide
MH  - MAP Kinase Signaling System
MH  - NG-Nitroarginine Methyl Ester
MH  - Nitric Oxide/metabolism
MH  - Oxidation-Reduction
MH  - Reactive Oxygen Species/metabolism
MH  - Respiratory Mucosa/cytology
MH  - Sodium Nitrite/*pharmacology
MH  - Wound Healing/*drug effects
PMC - PMC3854970
MID - NIHMS369475
EDAT- 2012/03/20 06:00
MHDA- 2012/12/14 06:00
PMCR- 2013/12/06
CRDT- 2012/03/20 06:00
PHST- 2011/08/29 00:00 [received]
PHST- 2012/02/09 00:00 [revised]
PHST- 2012/03/01 00:00 [accepted]
PHST- 2012/03/20 06:00 [entrez]
PHST- 2012/03/20 06:00 [pubmed]
PHST- 2012/12/14 06:00 [medline]
PHST- 2013/12/06 00:00 [pmc-release]
AID - S1089-8603(12)00036-5 [pii]
AID - 10.1016/j.niox.2012.03.002 [doi]
PST - ppublish
SO  - Nitric Oxide. 2012 May 15;26(4):203-10. doi: 10.1016/j.niox.2012.03.002. Epub 
      2012 Mar 8.