Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Loss of extracellular superoxide dismutase leads to acute lung damage in the presence of ambient air: a potential mechanism underlying adult respiratory distress syndrome.

The extracellular superoxide dismutase 3 (SOD3) is highly expressed in both blood vessels and lungs. In different models of pulmonary injury, SOD3 is reduced; however, it is unclear whether this contributes to lung injury. To study the role of acute SOD3 reduction in lung injury, the SOD3 gene was deleted in adult mice by using the Cre-Lox technology. Acute reduction of SOD3 led to a fivefold increase in lung superoxide, marked inflammatory cell infiltration, a threefold increase in the arterial-alveolar gradient, respiratory acidosis, histological changes similar to those observed in adult respiratory distress syndrome, and 85% mortality. Treatment with the SOD mimetic MnTBAP and intranasal administration of SOD-containing polyketal microparticles reduced mortality, prevented the histological alterations, and reduced lung superoxide levels. To understand how mice with the SOD3 embryonic deletion survived without lung injury, gene array analysis was performed. These data demonstrated the up-regulation of 37 genes and down-regulation of nine genes, including those involved in cell signaling, inflammation, and gene transcription in SOD3-/- mice compared with either mice with acute SOD3 reduction or wild-type controls. These studies show that SOD3 is essential for survival in the presence of ambient oxygen and that acute loss of this enzyme can lead to severe lung damage. Strategies either to prevent SOD3 inactivation or to augment its levels might prove useful in the treatment of acute lung injury.

Pubmed ID: 18787098 RIS Download

Mesh terms: Air | Animals | Aorta | Blood Gas Analysis | Blood Pressure | Extracellular Space | Gene Deletion | Heart Function Tests | Humans | Inflammation | Integrases | Lung | Metalloporphyrins | Mice | Mice, Inbred C57BL | Myocardium | Oligonucleotide Array Sequence Analysis | Respiratory Distress Syndrome, Adult | Superoxide Dismutase | Superoxides | Survival Analysis | Tamoxifen

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NHLBI NIH HHS, Id: HL390006
  • Agency: NHLBI NIH HHS, Id: U01 HL080711
  • Agency: NHLBI NIH HHS, Id: UO1 HL80711-01
  • Agency: NIBIB NIH HHS, Id: R21 EB006418
  • Agency: NHLBI NIH HHS, Id: HL59248
  • Agency: NHLBI NIH HHS, Id: P01 HL058000
  • Agency: NHLBI NIH HHS, Id: HL58000

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.