Mechanisms of myocardial membrane alterations in endotoxin shock: roles of phospholipase and phosphorylation.
Current progress in the studies of myocardial membrane alterations during endotoxin shock indicates that endotoxin administration impairs (Na(+) + K(+)-ATPase enzyme system by disrupting the coordination of the ouabain receptor subunit and the catalytic subunit of the enzyme system, and that the disruption is due to an alteration in the lipid microenvironment and a decrease in the phosphorylated intermediate of the enzyme cycle. Studies of the membrane lipid profile provide evidence that endotoxin administration modifies the molecular structure of cardiac membrane lipids in association with the activation of phospholipases A1 and A2 and with the inhibition of phospholipid methylating enzymes. Using liposomes as a membrane model for investigation, endotoxin was found to be capable of modifying the physical property of membrane phospholipids by altering the molecular packing and the phase transition temperature of lipid bilayers. Further studies with Na(+)-Ca2+ exchange system in cardiac sarcolemma have established the roles of phospholipase A2 and protein phosphorylation on the endotoxin-induced derangement in myocardial Na(+)-Ca2+ exchange. Based on these studies, it is concluded that endotoxin administration exerts multiple injuries in different membrane-associated enzyme/receptor systems and that the mechanisms responsible for the endotoxin-induced membrane damage can be categorized into two conceptual frameworks: namely, changes in membrane lipid microenvironment in response to phospholipase A activation and alterations in the phosphorylation of the enzyme/receptor proteins.
Liu
M S
MS
Department of Physiology, St. Louis University School of Medicine, MO 63104.
D000818:Animals; D004285:Dogs; D004731:Endotoxins / Q000097:blood; D006321:Heart / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology*; D010740:Phospholipases / Q000502:physiology*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000502:physiology; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D012508:Sarcolemma / Q000201:enzymology*; D012772:Shock, Septic / Q000201:enzymology*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
D004731:Endotoxins; D010743:Phospholipids; D012964:Sodium; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium