Phosphorylation of GSK-3β Mediates Intralipid-induced Cardioprotection against Ischemia/Reperfusion Injury

• DOI: 10.1097/aln.0b013e318223b8b9
• Publication Date: 2011-06-18T13:05:33Z
• Authors: Siamak Rahman; Jingyuan Li; Jean Chrisostome ...; Soban Umar; Andrea Iorga; Parisa Partownavid; Mansoureh Eghbali
• Keywords: Cardioprotection; Ex vivo

Background Intralipid (Sigma, St. Louis, MO), a brand name for the first safe fat emulsion human use, has been shown to be cardioprotective. However, mechanism of this protection is not known. The authors investigated molecular mechanism(s) Intralipid-induced cardioprotection against ischemia/reperfusion injury, particularly role glycogen synthase kinase-3β (GSK-3β) and mitochondrial permeability transition pore in protective action. Methods In vivo rat hearts or isolated Langendorff-perfused mouse were subjected ischemia followed by reperfusion with (1% ex one bolus 20% vivo) vehicle. hemodynamic function, infarct size, threshold opening pore, phosphorylation levels protein kinase B (Akt)/extracellular signal regulating (ERK)/GSK-3β measured. Results Administration at onset resulted approximately 70% reduction size model. also significantly improved functional recovery as rate pressure product was increased from 2,999 ± 863 mmHg*beats/min control group 13,676 611 (mean±SEM) markedly smaller (18.3 2.4% vs. 54.8 2.9% group, P < 0.01). fully abolished LY294002, specific inhibitor PI3K, but only partially PD98059, ERK inhibitor. Akt/ERK1/glycogen eightfold, threefold, ninefold, respectively. inhibited because calcium retention capacity higher (274.3 8.4 nM/mg 168.6 9.6 group). Conclusions Postischemic treatment inhibits mitochondiral protects heart through via PI3K/Akt/ERK pathways.