Heme oxygenase-1 protects against endotoxin-induced acute lung injury depends on NAD+-mediated mitonuclear communication through PGC1 α/PPARγ signaling pathway

In this study, we observed HO-1 attenuated endotoxin-induced ALI by regulated NAD+ levels and NAD+ affected the mitonuclear communication, including mitonuclear protein imbalance and UPRmt to alleviate lung damage. We also found the protective effect of HO-1 depended on NAD+ and NAD+-mediated mitonuclear communication. Furtherly, the inhibition of the PGC1 α/PPARγ signaling exacerbates the septic lung injury by reducing NAD+ levels and repressing the mitonuclear protein imbalance and UPRmt. Altogether, our study certified that HO-1 ameliorated endotoxin-induced acute lung injury by regulating NAD+ and NAD+-mediated mitonuclear communications through PGC1 α/PPARγ pathway. The present study provided complementary evidence for the cytoprotective effect of HO-1 as a potential target for preventing and attenuating of endotoxin-induced ALI.
Source: Inflammation Research - Category: Research Source Type: research