PGI synthase overexpression protects against bleomycin-induced mortality and is associated with increased Nqo 1 expression

Weisong Zhou; Dustin R. Dowell; Mark W. Geraci; Timothy S. Blackwell; Robert D. Collins; Vasiliy V. Polosukhin; William E. Lawson; Pingsheng Wu; Thomas E Sussan; Shyam Biswal; Kasia Goleniewska; Jamye O'Neal; Dawn C. Newcomb; Shinji Toki; Jason D. Morrow; Jr Stokes Peebles

doi:10.1152/ajplung.00224.2010

PGI synthase overexpression protects against bleomycin-induced mortality and is associated with increased Nqo 1 expression

Weisong Zhou, Dustin R. Dowell, Mark W. Geraci, Timothy S. Blackwell, Robert D. Collins, Vasiliy V. Polosukhin, William E. Lawson, Pingsheng Wu, Thomas E Sussan, Shyam Biswal, Kasia Goleniewska, Jamye O'Neal, Dawn C. Newcomb, Shinji Toki, Jason D. Morrow, Jr Stokes Peebles

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

The mortality rate for acute lung injury (ALI) is reported to be between 35-40%, and there are very few treatment strategies that improve the death rate from this condition. Previous studies have suggested that signaling through the prostaglandin (PG) I ₂ receptor may protect against bleomycin-induced ALI in mice. We found that mice that overexpress PGI synthase (PGIS) in the airway epithelium were significantly protected against bleomycin-induced mortality and had reduced parenchymal consolidation, apoptosis of lung tissue, and generation of F ₂-isoprostanes compared with littermate wild-type controls. In addition, we show for the first time in both in vivo and in vitro experiments that PGI ₂ induced the expression of NADP (H): quinoneoxidoreductase 1 (Nqo 1), an enzyme that prevents the generation of reactive oxygen species. PGI ₂ induction of Nqo 1 provides a possible novel mechanism by which this prostanoid protects against bleomycin-induced mortality and identifies a potential therapeutic target for human ALI.

Original language	English (US)
Pages (from-to)	L615-L622
Journal	American Journal of Physiology - Lung Cellular and Molecular Physiology
Volume	301
Issue number	4
DOIs	https://doi.org/10.1152/ajplung.00224.2010
State	Published - Oct 2011

Keywords

Epithelial cells
Lung
NAD(P)H: Quinoneoxidoreductase 1
Prostaglandin I

ASJC Scopus subject areas

Physiology
Pulmonary and Respiratory Medicine
Physiology (medical)
Cell Biology

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10.1152/ajplung.00224.2010

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Zhou, W., Dowell, D. R., Geraci, M. W., Blackwell, T. S., Collins, R. D., Polosukhin, V. V., Lawson, W. E., Wu, P., Sussan, T. E., Biswal, S., Goleniewska, K., O'Neal, J., Newcomb, D. C., Toki, S., Morrow, J. D., & Stokes Peebles, J. (2011). PGI synthase overexpression protects against bleomycin-induced mortality and is associated with increased Nqo 1 expression. American Journal of Physiology - Lung Cellular and Molecular Physiology, 301(4), L615-L622. https://doi.org/10.1152/ajplung.00224.2010

Zhou, W, Dowell, DR, Geraci, MW, Blackwell, TS, Collins, RD, Polosukhin, VV, Lawson, WE, Wu, P, Sussan, TE, Biswal, S, Goleniewska, K, O'Neal, J, Newcomb, DC, Toki, S, Morrow, JD & Stokes Peebles, J 2011, 'PGI synthase overexpression protects against bleomycin-induced mortality and is associated with increased Nqo 1 expression', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 301, no. 4, pp. L615-L622. https://doi.org/10.1152/ajplung.00224.2010

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title = "PGI synthase overexpression protects against bleomycin-induced mortality and is associated with increased Nqo 1 expression",

abstract = "The mortality rate for acute lung injury (ALI) is reported to be between 35-40%, and there are very few treatment strategies that improve the death rate from this condition. Previous studies have suggested that signaling through the prostaglandin (PG) I 2 receptor may protect against bleomycin-induced ALI in mice. We found that mice that overexpress PGI synthase (PGIS) in the airway epithelium were significantly protected against bleomycin-induced mortality and had reduced parenchymal consolidation, apoptosis of lung tissue, and generation of F 2-isoprostanes compared with littermate wild-type controls. In addition, we show for the first time in both in vivo and in vitro experiments that PGI 2 induced the expression of NADP (H): quinoneoxidoreductase 1 (Nqo 1), an enzyme that prevents the generation of reactive oxygen species. PGI 2 induction of Nqo 1 provides a possible novel mechanism by which this prostanoid protects against bleomycin-induced mortality and identifies a potential therapeutic target for human ALI.",

keywords = "Epithelial cells, Lung, NAD(P)H: Quinoneoxidoreductase 1, Prostaglandin I",

author = "Weisong Zhou and Dowell, {Dustin R.} and Geraci, {Mark W.} and Blackwell, {Timothy S.} and Collins, {Robert D.} and Polosukhin, {Vasiliy V.} and Lawson, {William E.} and Pingsheng Wu and Sussan, {Thomas E} and Shyam Biswal and Kasia Goleniewska and Jamye O'Neal and Newcomb, {Dawn C.} and Shinji Toki and Morrow, {Jason D.} and {Stokes Peebles}, Jr",

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AU - Geraci, Mark W.

AU - Blackwell, Timothy S.

AU - Collins, Robert D.

AU - Polosukhin, Vasiliy V.

AU - Lawson, William E.

AU - Wu, Pingsheng

AU - Sussan, Thomas E

AU - Biswal, Shyam

AU - Goleniewska, Kasia

AU - O'Neal, Jamye

AU - Newcomb, Dawn C.

AU - Toki, Shinji

AU - Morrow, Jason D.

AU - Stokes Peebles, Jr

PY - 2011/10

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N2 - The mortality rate for acute lung injury (ALI) is reported to be between 35-40%, and there are very few treatment strategies that improve the death rate from this condition. Previous studies have suggested that signaling through the prostaglandin (PG) I 2 receptor may protect against bleomycin-induced ALI in mice. We found that mice that overexpress PGI synthase (PGIS) in the airway epithelium were significantly protected against bleomycin-induced mortality and had reduced parenchymal consolidation, apoptosis of lung tissue, and generation of F 2-isoprostanes compared with littermate wild-type controls. In addition, we show for the first time in both in vivo and in vitro experiments that PGI 2 induced the expression of NADP (H): quinoneoxidoreductase 1 (Nqo 1), an enzyme that prevents the generation of reactive oxygen species. PGI 2 induction of Nqo 1 provides a possible novel mechanism by which this prostanoid protects against bleomycin-induced mortality and identifies a potential therapeutic target for human ALI.

AB - The mortality rate for acute lung injury (ALI) is reported to be between 35-40%, and there are very few treatment strategies that improve the death rate from this condition. Previous studies have suggested that signaling through the prostaglandin (PG) I 2 receptor may protect against bleomycin-induced ALI in mice. We found that mice that overexpress PGI synthase (PGIS) in the airway epithelium were significantly protected against bleomycin-induced mortality and had reduced parenchymal consolidation, apoptosis of lung tissue, and generation of F 2-isoprostanes compared with littermate wild-type controls. In addition, we show for the first time in both in vivo and in vitro experiments that PGI 2 induced the expression of NADP (H): quinoneoxidoreductase 1 (Nqo 1), an enzyme that prevents the generation of reactive oxygen species. PGI 2 induction of Nqo 1 provides a possible novel mechanism by which this prostanoid protects against bleomycin-induced mortality and identifies a potential therapeutic target for human ALI.

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KW - Lung

KW - NAD(P)H: Quinoneoxidoreductase 1

KW - Prostaglandin I

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PGI synthase overexpression protects against bleomycin-induced mortality and is associated with increased Nqo 1 expression

Abstract

Keywords

ASJC Scopus subject areas

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