Premium
Mechanosensing with restart of flow drives K ATP channel induced NOX2 activation in a model of Lung Ischemia Reperfusion
Author(s) -
Chatterjee Shampa,
Wang Hui,
Hong Nankang,
Yu Kevin,
Debolt Kristine,
Feinstein Sheldon I,
Christie Jason D,
Cantu Edward,
Fisher Aron B
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.913.19
Subject(s) - ischemia , reperfusion injury , lung , reactive oxygen species , chemistry , lung transplantation , medicine , pharmacology , microbiology and biotechnology , biology , biochemistry
From our earlier studies in lung ischemia, we concluded that endothelial mechanotransduction with stop of flow in the lung activates the generation of reactive oxygen species (ROS) as a result of K ATP closure that leads to NOX2 activation. As the next phase, we evaluated the role of mechanosignaling with reperfusion (I/R). We now propose that the increase in shear with reperfusion triggers a mechanosignaling cascade similar to that associated with ischemia. Isolated perfused mouse lungs and pulmonary endothelial cells showed a 2 fold increase in ROS production (as monitored by ROS sensitive dyes H 2 DCFDA, H 2 DFFDA and DHE) with ischemia that is further enhanced by 3–3.5 fold upon reperfusion. This was not observed in lungs from K ATP channel null and NOX2 mice. Lungs subjected to ischemia or I/R show ~1.8 fold increase in lung damage (as assessed by 8‐isoprostanes, TBARS, permeability) with ischemia and a ~2.5 fold increase during the reperfusion period. Understanding the initiation of reperfusion signaling has potential application in lung transplantation which requires reperfusion of a previously ischemic lung; thus this model is relevant to design strategies that can reduce NOX2 activation and resultant injury.