Contribution of PPAR alpha/beta/gamma, AP-1, importin-alpha 3, and RXR alpha to the protective effect of 5,14-HEDGE, a 20-HETE mimetic, against hypotension, tachycardia, and inflammation in a rat model of septic shock

摘要

We have previously demonstrated that downregulation of the MyD88/TAK1-dependent signaling pathway associated with increased CYP4A1 expression and 20-HETE formation participates in the protective effect of N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE), a 20-HETE mimetic, against vascular hyporeactivity, hypotension, tachycardia, inflammation, and mortality in a rodent model of septic shock. The aim of this study was to determine whether increased renal and cardiovascular expression of PPAR alpha/beta/gamma and RXR alpha associated with decreased expression and/or activity of AP-1 and importin-alpha 3 participates in the protective effect of 5,14-HEDGE in response to systemic administration of lipopolysaccharide (LPS).