PMID- 24696144
OWN - NLM
STAT- MEDLINE
DCOM- 20140717
LR  - 20211021
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 306
IP  - 11
DP  - 2014 Jun 1
TI  - Dysregulation of CLOCK gene expression in hyperoxia-induced lung injury.
PG  - C999-C1007
LID - 10.1152/ajpcell.00064.2013 [doi]
AB  - Hyperoxic acute lung injury (HALI) is characterized by inflammation and 
      epithelial cell death. CLOCK genes are master regulators of circadian rhythm also 
      implicated in inflammation and lung diseases. However, the relationship of CLOCK 
      genes in hyperoxia-induced lung injury has not been studied. This study will 
      determine if HALI alters CLOCK gene expression. To test this, wild-type and 
      NALP3(-/-) mice were exposed to room air or hyperoxia for 24, 48, or 72 h. In 
      addition, mice were exposed to different concentrations of hyperoxia (50, 75, or 
      100% O2) or room air for 72 h. The mRNA and protein levels of lung CLOCK genes, 
      based on quantitative PCR and Western blot analysis, respectively, and their 
      target genes are significantly elevated in mice exposed to hyperoxia compared 
      with controls. Alterations in CLOCK genes are associated with increased 
      inflammatory markers in bronchoalveolar lavage fluid of hyperoxic mice compared 
      with controls. Histological examination of mice lungs exposed to hyperoxia show 
      increased inflammation and alveolar congestion compared with controls. Our 
      results indicate sequential increase in CLOCK gene expression in lungs of mice 
      exposed to hyperoxia compared with controls. Additionally, data suggest a 
      dose-dependent increase in CLOCK gene expression with increased oxygen 
      concentrations. To validate if the expression changes related to CLOCK genes are 
      indeed associated with inflammation, NALP3(-/-) was introduced to analyze loss of 
      function in inflammation. Western blot analysis showed significant CLOCK gene 
      downregulation in NALP3(-/-) mice compared with wild-type controls. Together, our 
      results demonstrate that hyperoxia-mediated lung inflammation is associated with 
      alterations in CLOCK gene expression.
CI  - Copyright (c) 2014 the American Physiological Society.
FAU - Lagishetty, Venu
AU  - Lagishetty V
AD  - Division of Allergy and Immunology, Internal Medicine, Morsani College of 
      Medicine, University of South Florida, Tampa, Florida.
FAU - Parthasarathy, Prasanna Tamarapu
AU  - Parthasarathy PT
AD  - Division of Allergy and Immunology, Internal Medicine, Morsani College of 
      Medicine, University of South Florida, Tampa, Florida.
FAU - Phillips, Oluwakemi
AU  - Phillips O
AD  - Division of Allergy and Immunology, Internal Medicine, Morsani College of 
      Medicine, University of South Florida, Tampa, Florida.
FAU - Fukumoto, Jutaro
AU  - Fukumoto J
AD  - Division of Allergy and Immunology, Internal Medicine, Morsani College of 
      Medicine, University of South Florida, Tampa, Florida.
FAU - Cho, Young
AU  - Cho Y
AD  - Division of Allergy and Immunology, Internal Medicine, Morsani College of 
      Medicine, University of South Florida, Tampa, Florida.
FAU - Fukumoto, Itsuko
AU  - Fukumoto I
AD  - Division of Allergy and Immunology, Internal Medicine, Morsani College of 
      Medicine, University of South Florida, Tampa, Florida.
FAU - Bao, Huynh
AU  - Bao H
AD  - Division of Allergy and Immunology, Internal Medicine, Morsani College of 
      Medicine, University of South Florida, Tampa, Florida.
FAU - Cox, Ruan Jr
AU  - Cox R Jr
AD  - Division of Allergy and Immunology, Internal Medicine, Morsani College of 
      Medicine, University of South Florida, Tampa, Florida.
FAU - Galam, Lakshmi
AU  - Galam L
AD  - Division of Allergy and Immunology, Internal Medicine, Morsani College of 
      Medicine, University of South Florida, Tampa, Florida.
FAU - Lockey, Richard F
AU  - Lockey RF
AD  - Division of Allergy and Immunology, Internal Medicine, Morsani College of 
      Medicine, University of South Florida, Tampa, Florida.
FAU - Kolliputi, Narasaiah
AU  - Kolliputi N
AD  - Division of Allergy and Immunology, Internal Medicine, Morsani College of 
      Medicine, University of South Florida, Tampa, Florida nkollipu@health.usf.edu.
LA  - eng
GR  - R01 HL105932/HL/NHLBI NIH HHS/United States
GR  - R01-HL-105932/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 - 20140402
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (RNA, Messenger)
RN  - EC 2.3.1.48 (CLOCK Proteins)
RN  - EC 2.3.1.48 (Clock protein, mouse)
SB  - IM
MH  - Animals
MH  - CLOCK Proteins/*biosynthesis/genetics
MH  - *Gene Expression Regulation
MH  - Hyperoxia/genetics/*metabolism/pathology
MH  - Lung Injury/genetics/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - RNA, Messenger/biosynthesis/genetics
PMC - PMC4042094
OTO - NOTNLM
OT  - acute lung injury
OT  - circadian rhythms
OT  - hyperoxia
OT  - inflammation
EDAT- 2014/04/04 06:00
MHDA- 2014/07/18 06:00
PMCR- 2015/06/01
CRDT- 2014/04/04 06:00
PHST- 2014/04/04 06:00 [entrez]
PHST- 2014/04/04 06:00 [pubmed]
PHST- 2014/07/18 06:00 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - ajpcell.00064.2013 [pii]
AID - C-00064-2013 [pii]
AID - 10.1152/ajpcell.00064.2013 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2014 Jun 1;306(11):C999-C1007. doi: 
      10.1152/ajpcell.00064.2013. Epub 2014 Apr 2.