PLA2dependence of diaphragm mitochondrial formation of reactive oxygen species

• DOI: 10.1152/jappl.2000.89.1.72
• Publication Date: 2017-12-23T01:59:59Z
• Authors: D. Nethery; L. A. Callahan; D. Stofan; R. Mattera; A DiMarco; G. Supinski
• Keywords: Mitochondrial ROS

Contraction-induced respiratory muscle fatigue and sepsis-related reductions in force-generating capacity are mediated, at least part, by reactive oxygen species (ROS). The subcellular sources mechanisms of generation ROS these conditions incompletely understood. We postulated that the physiological changes associated with contraction (i.e., increases calcium ADP concentration) stimulate mitochondrial a phospholipase A(2) (PLA(2))-modulated process sepsis enhances upregulating PLA(2) activity. To test hypotheses, we examined H(2)O(2) diaphragm mitochondria isolated from saline-treated control endotoxin-treated septic animals presence absence ADP; also assessed effect inhibitors on formation. found 1) stimulated formation both animals; 2) demonstrated substantially higher than under basal, calcium-stimulated, ADP-stimulated conditions; 3) 14-kDa blocked enhanced all conditions. administration arachidonic acid (the principal metabolic product activation) increased interacting complex I electron transport chain. These data suggest during may be critically dependent activation.