The serpentine path to a novel mechanism-based inhibitor of acute inflammatory lung injury.

Abstract

The Comroe lecture on which this review is based described my research path during the past 45 years, beginning with studies of oxidant stress (hyperoxia) and eventuating in the discovery of a synthetic inhibitor of phospholipase A2 activity (called MJ33) that prevents acute lung injury in mice exposed to lipopolysaccharide. In between were studies of lung ischemia, lung surfactant metabolism, the protein peroxiredoxin 6 and its phospholipase A2 activity, and mechanisms for NADPH oxidase activation. These seemingly unrelated research activities provided the nexus for identification of a novel target and a potentially novel therapeutic agent for prevention or treatment of acute lung injury.

• Authors: Aron B Fisher
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 116 Issue 12 Pg. 1521-30 (Jun 15 2014) ISSN: 1522-1601 [Electronic] United States
• PMID: 24744383 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright © 2014 the American Physiological Society.

Chemical References

• Peroxiredoxin VI
• NADPH Oxidases
• Phospholipases A2

Topics

• Acute Lung Injury (metabolism, physiopathology)
• Animals
• Humans
• Inflammation (metabolism, physiopathology)
• NADPH Oxidases (metabolism)
• Oxidative Stress (physiology)
• Peroxiredoxin VI (metabolism)
• Phospholipases A2 (metabolism)