PMID- 15841185
OWN - NLM
STAT- MEDLINE
DCOM- 20050628
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 115
IP  - 4
DP  - 2005 Apr
TI  - Bcl-2-related protein A1 is an endogenous and cytokine-stimulated mediator of 
      cytoprotection in hyperoxic acute lung injury.
PG  - 1039-48
AB  - Hyperoxic acute lung injury (HALI) is characterized by a cell death response with 
      features of apoptosis and necrosis that is inhibited by IL-11 and other 
      interventions. We hypothesized that Bfl-1/A1, an antiapoptotic Bcl-2 protein, is 
      a critical regulator of HALI and a mediator of IL-11-induced cytoprotection. To 
      test this, we characterized the expression of A1 and the oxygen susceptibility of 
      WT and IL-11 Tg(+) mice with normal and null A1 loci. In WT mice, 100% O(2) 
      caused TUNEL(+) cell death, induction and activation of intrinsic and 
      mitochondrial-death pathways, and alveolar protein leak. Bcl-2 and Bcl-xl were 
      also induced as an apparent protective response. A1 was induced in hyperoxia, and 
      in A1-null mice, the toxic effects of hyperoxia were exaggerated, Bcl-2 and 
      Bcl-xl were not induced, and premature death was seen. In contrast, IL-11 
      stimulated A1, diminished the toxic effects of hyperoxia, stimulated Bcl-2 and 
      Bcl-xl, and enhanced murine survival in 100% O(2). In A1-null mice, IL-11-induced 
      protection, survival advantage, and Bcl-2 and Bcl-xl induction were significantly 
      decreased. VEGF also conferred protection via an A1-dependent mechanism. In vitro 
      hyperoxia also stimulated A1, and A1 overexpression inhibited oxidant-induced 
      epithelial cell apoptosis and necrosis. A1 is an important regulator of 
      oxidant-induced lung injury, apoptosis, necrosis, and Bcl-2 and Bcl-xl gene 
      expression and a critical mediator of IL-11- and VEGF-induced cytoprotection.
FAU - He, Chuan Hua
AU  - He CH
AD  - Department of Internal Medicine, Section of Pulmonary and Critical Care Medicine, 
      Yale University School of Medicine, New Haven, Connecticut 06520-8057, USA.
FAU - Waxman, Aaron B
AU  - Waxman AB
FAU - Lee, Chun Geun
AU  - Lee CG
FAU - Link, Holger
AU  - Link H
FAU - Rabach, Morgan E
AU  - Rabach ME
FAU - Ma, Bing
AU  - Ma B
FAU - Chen, Qingsheng
AU  - Chen Q
FAU - Zhu, Zhou
AU  - Zhu Z
FAU - Zhong, Mei
AU  - Zhong M
FAU - Nakayama, Keiko
AU  - Nakayama K
FAU - Nakayama, Keiichi I
AU  - Nakayama KI
FAU - Homer, Robert
AU  - Homer R
FAU - Elias, Jack A
AU  - Elias JA
LA  - eng
GR  - AR46032/AR/NIAMS NIH HHS/United States
GR  - R01HL064242-05/HL/NHLBI NIH HHS/United States
GR  - P30 AR046032/AR/NIAMS NIH HHS/United States
GR  - P01 HL056389/HL/NHLBI NIH HHS/United States
GR  - R01 HL064242/HL/NHLBI NIH HHS/United States
GR  - R01 HL078744/HL/NHLBI NIH HHS/United States
GR  - 1R01HL078744-01/HL/NHLBI NIH HHS/United States
GR  - 5P01HL56389-08/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Interleukin-11)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 3.4.22.- (Caspases)
RN  - S88TT14065 (Oxygen)
SB  - IM
CIN - J Clin Invest. 2005 Apr;115(4):828-30. PMID: 15841170
MH  - Animals
MH  - Caspases/metabolism
MH  - Cell Death/physiology
MH  - Cells, Cultured
MH  - In Situ Nick-End Labeling
MH  - Interleukin-11/genetics/metabolism
MH  - Lung/cytology/*immunology/pathology
MH  - Lung Diseases/*immunology/pathology
MH  - *Lung Injury
MH  - Mice
MH  - Mice, Transgenic
MH  - Oxygen/*metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism
MH  - Survival Rate
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC1070412
EDAT- 2005/04/21 09:00
MHDA- 2005/06/29 09:00
PMCR- 2005/04/01
CRDT- 2005/04/21 09:00
PHST- 2004/08/11 00:00 [received]
PHST- 2005/01/04 00:00 [accepted]
PHST- 2005/04/21 09:00 [pubmed]
PHST- 2005/06/29 09:00 [medline]
PHST- 2005/04/21 09:00 [entrez]
PHST- 2005/04/01 00:00 [pmc-release]
AID - 23004 [pii]
AID - 10.1172/JCI23004 [doi]
PST - ppublish
SO  - J Clin Invest. 2005 Apr;115(4):1039-48. doi: 10.1172/JCI23004.