Pgc-1 α Promotes Phosphorylation, Inflammation, and Apoptosis in H9c2 Cells During the Early Stage of Lipopolysaccharide Induction

AbstractCardiac dysfunction in severe sepsis is associated with increased mortality. However, the molecular mechanisms underlying septic heart dysfunction remain unclear. Expression of peroxisome proliferator-activated receptor- γ coactivator 1α (Pgc-1α), concentrations of inflammatory factors, and activation of the nuclear factor kappa-B (NF-κB) signaling pathway were examined in H9c2 cells after a 24-h lipopolysaccharide (LPS) stimulation period using qPCR, enzyme-linked immunosorbent assays (ELISAs), and western blot s (WBs), respectively. Pgc-1α was overexpressed and suppressed in cells using a lentivirus vector and siRNA, respectively. The effects of Pgc-1α dysfunction on the release of inflammatory factors and apoptosis were analyzed. Pgc-1α expression was increased after LPS induction for 0.5 h and return ed to the pre-induction level at 2 h. Levels of IL-1β, IL-6, and TNF-α increase after LPS induction for 0.5 h and accumulated in the culture supernatants over time. The WBs revealed the highest Pgc-1α and phospho (p)-p65 protein levels after LPS induction for 0.5 h, followed by a decrease; moreov er, the cleaved-caspase-3 level increased after LPS induction for 0.5 h and increased gradually thereafter. A functional analysis of Pgc-1α revealed that overexpression of this protein enhanced LPS-induced inflammatory factors and p-p65 levels and inhibited apoptosis during the early stage after LP S induction (0.5 and 4 h). In contrast, the inhibition of Pgc-1α e...
Source: Inflammation - Category: Allergy & Immunology Source Type: research