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


METHODS
Body temperature of rats was elevated to 42 degrees 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.


RESULTS
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.


CONCLUSIONS
Heat stress preserves bile acid transporters during endotoxemia by a posttranscriptional mechanism.
Bolder
Ulrich
U
Department of Surgery, University of Regensburg, Regensburg, Germany. ulrich_bolder@yahoo.com
Schmidt
Andrea
A
Landmann
Lukas
L
Kidder
Verena
V
Tange
Stefan
S
Jauch
Karl-Walter
KW
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D018882:Heat Stress Disorders / Q000378:metabolism*; D006360:Heat-Shock Proteins; D022781:Hepatocytes / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins / Q000032:analysis; D029363:Organic Anion Transporters, Sodium-Dependent; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000737:chemistry; D027981:Symporters
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490548:Abcb11 protein, rat; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D027981:Symporters; C071908:sodium-bile acid cotransporter