PMID- 18718025
OWN - NLM
STAT- MEDLINE
DCOM- 20090519
LR  - 20211020
IS  - 1466-609X (Electronic)
IS  - 1364-8535 (Print)
IS  - 1364-8535 (Linking)
VI  - 12
IP  - 4
DP  - 2008
TI  - Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in 
      ventilator-induced lung injury.
PG  - R108
LID - 10.1186/cc6995 [doi]
AB  - INTRODUCTION: Poly (ADP-ribose) polymerase (PARP) participates in inflammation by 
      cellular necrosis and the nuclear factor-kappa-B (NF-kappaB)-dependent 
      transcription. The purpose of this study was to examine the roles of PARP in 
      ventilator-induced lung injury (VILI) in normal mice lung. METHODS: Male C57BL/6 
      mice were divided into four groups: sham tracheostomized (sham), lung-protective 
      ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment 
      (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory 
      pressure (PIP) 15 cm H2O + positive end-expiratory pressure (PEEP) 3 cm H2O + 90 
      breaths per minute for the LPV group and PIP 40 cm H2O + PEEP 0 cm H2O + 90 
      breaths per minute for the VILI and PJ34+VILI groups. After 2 hours of MV, acute 
      lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and 
      dynamic compliance (CD) were recorded. Tumor necrosis factor-alpha (TNF-alpha), 
      interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX) 
      in the bronchoalveolar lavage fluid and NF-kappaB DNA-binding activity in tissue 
      homogenates were measured. RESULTS: The VILI group showed higher ALI score, W/D 
      weight ratio, MPO activity, NOX, and concentrations of TNF-alpha and IL-6 along 
      with lower CD than the sham and LPV groups (P < 0.05). In the PJ34+VILI group, 
      PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and 
      pulmonary dynamics (P < 0.05). NF-kappaB activity was increased in the VILI group 
      as compared with the sham and LPV groups (P < 0.05) and was decreased in the 
      PJ34+VILI group as compared with the VILI group (P = 0.009). Changes in all 
      parameters were closely correlated with the PARP activity (P < 0.05). CONCLUSION: 
      Overactivation of PARP plays an important role in the inflammatory and 
      transcriptional pathogenesis of VILI, and PARP inhibition has potentially 
      beneficial effects on the prevention and treatment of VILI.
FAU - Kim, Je Hyeong
AU  - Kim JH
AD  - Division of Pulmonary, Sleep and Critical Care Medicine, Department of Internal 
      Medicine, Korea University Ansan Hospital, 516, Gojan 1-dong, Danwon-gu, Ansan 
      425-707, Republic of Korea.
FAU - Suk, Min Hyun
AU  - Suk MH
FAU - Yoon, Dae Wui
AU  - Yoon DW
FAU - Kim, Hye Young
AU  - Kim HY
FAU - Jung, Ki Hwan
AU  - Jung KH
FAU - Kang, Eun Hae
AU  - Kang EH
FAU - Lee, Sung Yong
AU  - Lee SY
FAU - Lee, Sang Yeub
AU  - Lee SY
FAU - Suh, In Bum
AU  - Suh IB
FAU - Shin, Chol
AU  - Shin C
FAU - Shim, Jae Jeong
AU  - Shim JJ
FAU - In, Kwang Ho
AU  - In KH
FAU - Yoo, Se Hwa
AU  - Yoo SH
FAU - Kang, Kyung Ho
AU  - Kang KH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080822
PL  - England
TA  - Crit Care
JT  - Critical care (London, England)
JID - 9801902
RN  - 0 (Inflammation Mediators)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
SB  - IM
CIN - Crit Care. 2008;12(5):431. PMID: 18983699
MH  - Animals
MH  - Enzyme Activation/physiology
MH  - Inflammation Mediators/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Poly(ADP-ribose) Polymerases/genetics/*physiology
MH  - Respiration, Artificial/*adverse effects
MH  - Transcription, Genetic/genetics/*physiology
MH  - Ventilator-Induced Lung Injury/*enzymology/etiology/pathology
PMC - PMC2575597
EDAT- 2008/08/23 09:00
MHDA- 2009/05/20 09:00
PMCR- 2008/08/22
CRDT- 2008/08/23 09:00
PHST- 2008/03/25 00:00 [received]
PHST- 2008/07/14 00:00 [revised]
PHST- 2008/08/22 00:00 [accepted]
PHST- 2008/08/23 09:00 [pubmed]
PHST- 2009/05/20 09:00 [medline]
PHST- 2008/08/23 09:00 [entrez]
PHST- 2008/08/22 00:00 [pmc-release]
AID - cc6995 [pii]
AID - 10.1186/cc6995 [doi]
PST - ppublish
SO  - Crit Care. 2008;12(4):R108. doi: 10.1186/cc6995. Epub 2008 Aug 22.