Within Endotoxin Shock Dog Liver Protein Kinase C, Calcium, Calmodulin-dependent Protein Kinase And Protein Kinase A Enzyme Kinetics Change

Septic shock is a frequent clinical syndrome. Despite the use of specific antibiotic, careful monitoring and aggressive operative intervention, septic shock continues to cause the higher mortality in clinical medicine today. Septic shock is characterized by a number of hemodynamic and metabolic disturbances. As the shock progresses, the tissues of many vital organs are damaged and eventual multiple organ failure develops. The precise cellular and molecular mechanisms for these derangements have, until recently, remained obscure. Since it is now believed that liver dysfunction in septic shock plays a fundamental role in metabolic alteration, and is an important factor in determining the fate of shock patients, an understanding of the mechanism responsible for the liver dysfunction would provide a biochemical basis for the better management of shock. Hepatic metabolism are controlled by hormones and agents using two different signal transduction pathways, i.e., regulating intracellular levels of either cAMP or DG and Ca2+. These second messengers activate different protein kinases and hence regulate metabolism and other processes by phosphorylating a number of cellular regulatory enzymes and receptor proteins. Previous studies have shown that liver dysfunction is related to impaired signal transduction pathways in endotoxic shock, but the results are contradictory in determining which point at the pathway is altered, and the changes of hepatic protein kinase activities in endotoxic shock are not reported. In the present experiments, therefore, we systemically investigate the effects of endotoxin administration on kinetic characteristics of three protein kinases in canine liver, in an attempt to understand the pathophysiology of altered hepatic metabolism and other processes in endotoxic shock. These enzymes include protein kinase C (PKC), Ca2+/caM kinase and protein kinase A (PKA) respectivelyI. Effects of endotoxin administration on the kinetic changes of PKC in canine liver1. Purification and assay of hepatic PKC. Male mongrel dogs, weighing from 15 to 20 kg, were employed and were randomly divided into two groups: control and endotoxic. Endotoxic group was given a single intravenous injection of 0.5mg/kg endotoxin from Escherichia coli. The endotoxin-injected dogs exhibited a shock...