Heat stress prevents impairment of bile acid transport in endotoxemic rats by a posttranscriptional mechanism

Endotoxemia leads to reduction of bile acid transporters in the hepatocyte membrane and impaired bile acid transport. Because heat stress ameliorates other sequelae of endotoxemia, studies were performed to determine whether heat stress would correct deficient bile acid transport caused by endotoxin. Body temperature of rats was elevated to 42°C for 10 minutes. Lipopolysaccharide was injected after different time intervals, and maximal transport for cholyltaurine was measured in perfused rat livers. Sodium-dependent and -independent uptake was studied in isolated hepatocytes. Protein expression, messenger RNA levels, and tissue distribution of the bile acid transporters sodium taurocholate cotransporting protein (ntcp) and bile salt export pump (bsep) were also analyzed. In the perfused liver, cholyltaurine transport was reduced by 59% by endotoxin, but transport was not reduced when heat stress was applied 2 hours before injection of Lipopolysaccharide. The protective effect coincided with maximal expression of heat shock proteins 70 and 25. Sodium-dependent and -independent transport was preserved by heat stress. Expression of bile acid transporters in plasma membrane fractions was reduced after injection of lipopolysaccharide but not if Lipopolysaccharide was preceded by heat stress. In contrast, messenger RNA levels of bile acid transporters were not preserved by heat stress. Heat stress preserves bile acid transporters during endotoxemia by a posttranscriptional mechanism.