PMID- 21906671
OWN - NLM
STAT- MEDLINE
DCOM- 20120210
LR  - 20211020
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 51
IP  - 10
DP  - 2011 Nov 15
TI  - Omeprazole attenuates hyperoxic injury in H441 cells via the aryl hydrocarbon 
      receptor.
PG  - 1910-7
LID - 10.1016/j.freeradbiomed.2011.08.013 [doi]
AB  - Hyperoxia contributes to the development of bronchopulmonary dysplasia in 
      premature infants. Earlier we observed that aryl hydrocarbon receptor 
      (AhR)-deficient mice are more susceptible to hyperoxic lung injury than 
      AhR-sufficient mice, and this phenomenon was associated with a lack of expression 
      of cytochrome P450 1A enzymes. Omeprazole, a proton pump inhibitor used in humans 
      with gastric acid-related disorders, activates AhR in hepatocytes in vitro. 
      However, the effects of omeprazole on AhR activation in the lungs and its impact 
      on hyperoxia-induced reactive oxygen species (ROS) generation and inflammation 
      are unknown. In this study, we tested the hypothesis that omeprazole attenuates 
      hyperoxia-induced cytotoxicity, ROS generation, and expression of monocyte 
      chemoattractant protein-1 (MCP-1) in human lung-derived H441 cells via AhR 
      activation. Experimental groups included cells transfected with AhR small 
      interfering RNA (siRNA). Hyperoxia resulted in significant increases in 
      cytotoxicity, ROS generation, and MCP-1 production, which were significantly 
      attenuated with the functional activation of AhR by omeprazole. The protective 
      effects of omeprazole on cytotoxicity, ROS production, and MCP-1 production were 
      lost in H441 cells whose AhR gene was silenced by AhR siRNA. These findings 
      support the hypothesis that omeprazole protects against hyperoxic injury in vitro 
      via AhR activation that is associated with decreased ROS generation and 
      expression of MCP-1.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Shivanna, Binoy
AU  - Shivanna B
AD  - Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Texas 
      Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA. 
      shivanna@bcm.edu
FAU - Chu, Chun
AU  - Chu C
FAU - Welty, Stephen E
AU  - Welty SE
FAU - Jiang, Weiwu
AU  - Jiang W
FAU - Wang, Lihua
AU  - Wang L
FAU - Couroucli, Xanthi I
AU  - Couroucli XI
FAU - Moorthy, Bhagavatula
AU  - Moorthy B
LA  - eng
GR  - R01 ES009132/ES/NIEHS NIH HHS/United States
GR  - R01 ES019689/ES/NIEHS NIH HHS/United States
GR  - HL-087174/HL/NHLBI NIH HHS/United States
GR  - ES-019689/ES/NIEHS NIH HHS/United States
GR  - R01 HL087174/HL/NHLBI NIH HHS/United States
GR  - ES-009132/ES/NIEHS NIH HHS/United States
GR  - R01 HL070921/HL/NHLBI NIH HHS/United States
GR  - HL-070921/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110823
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - KG60484QX9 (Omeprazole)
SB  - IM
MH  - Anti-Inflammatory Agents/*administration & dosage/adverse effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Chemokine CCL2/genetics/metabolism
MH  - Cytoprotection/drug effects
MH  - Epithelial Cells/*drug effects/metabolism/pathology
MH  - Gene Expression Regulation/drug effects/immunology
MH  - Humans
MH  - Hyperoxia/*drug therapy/pathology/physiopathology
MH  - Lung/pathology
MH  - Lung Injury/prevention & control
MH  - Omeprazole/*administration & dosage/adverse effects
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Aryl Hydrocarbon/immunology/*metabolism
PMC - PMC3901644
MID - NIHMS495575
EDAT- 2011/09/13 06:00
MHDA- 2012/02/11 06:00
PMCR- 2014/01/24
CRDT- 2011/09/13 06:00
PHST- 2011/04/22 00:00 [received]
PHST- 2011/08/16 00:00 [revised]
PHST- 2011/08/17 00:00 [accepted]
PHST- 2011/09/13 06:00 [entrez]
PHST- 2011/09/13 06:00 [pubmed]
PHST- 2012/02/11 06:00 [medline]
PHST- 2014/01/24 00:00 [pmc-release]
AID - S0891-5849(11)00522-3 [pii]
AID - 10.1016/j.freeradbiomed.2011.08.013 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2011 Nov 15;51(10):1910-7. doi: 
      10.1016/j.freeradbiomed.2011.08.013. Epub 2011 Aug 23.