Fig. 7.  Proposed mechanisms underlying Intralipid-induced cardioprotection against ischemia/reperfusion injury. The Reperfusion Injury Salvage Kinases (RISK) pathway is activated in the presence of Intralipid (ILP), resulting in increased phosphorylation of both protein kinase B (Akt) and extracellular signal-regulating kinase (ERK), although the degree of activation is much more prounnced in Akt (eightfold, thick arrow ) than in ERK (threefold, thin arrow ). Both pathways converge to phosphorylate glycogen synthase kinase-3β (GSK-3β, inactive form), which in turn inhibits the opening of the mitochondrial permeability transition core (mPTP) and induces protection against reperfusion injury. The protection provided by Intralipid is fully abolished by the PI3K-specific inhibitor, LY294002 (LY), and partially by PD98059 (PD). MEK = mitogen-activated protein kinases kinase.