fig 9.
Schematic Rac1 signalling pathway leading to cardiomyocyte TNF-α expression and cardiac dysfunction during LPS stimulation. LPS activates Rac1 via TLR4/PI3K/PtdIns(3,4,5)P3/GEF signalling. Activation of Rac1 activates NADPH oxidase leading to production of O2−, phosphorylation of ERK1/2 MAPK, and expression of TNF-α. Increased myocardial TNF-α production results in cardiac dysfunction during endotoxemia. TLR4: toll-like receptor 4; GEF: guanine nucleotide exchange factor; GAP: GTPase-activating proteins.