Lipopolysaccharide decreasing albumin expression in rat hepatocytes.
BACKGROUND
The relations of the severity of hypoalbuminemia to morbidity and mortality of patients with critical illness illustrate the need for better understanding of molecular mechanism of hypoalbuminemia. This study was undertaken to investigate the response of albumin synthesis to lipopolysaccharide (LPS)in rat hepatocytes in vitro in early acute phase of sepsis.


METHODS
Hepatocytes were cultured at an initial cell density of 1.5 x 10(6) cells/well in 3 ml culture medium. There were two groups of samples which received either normal saline or 1 microg/L LPS randomly. Albumin mRNA in hepatocytes was assessed by reverse transcription-polymerase chain reaction (RT-PCR)and albumin level in the supernatant was measured by ELISA at 0, 2, 8, 12, 24 hours after exposure. Meanwhile, the albumin precursor was evaluated at the same time points by flow cytometry.


RESULTS
The quantitative changes of mRNA,albumin precursor and its protein were analogous. All of them tended to decline at 12 hours post-treatment and did not decrease significantly until 24 hours after LPS exposure. Meanwhile, albumin mRNA decreased about 30% and the levels of albumin precursor and albumin reduced approximately 50%.


CONCLUSIONS
LPS can inhibit albumin synthesis in rat hepatocytes by prevention of albumin transcription. Moreover, the response of hepatic albumin synthesis to LPS changes with the stage of sepsis process. The results show that albumin metabolism in sepsis is a complicated process and further studies are required to understand the molecular mechanism of LPS-induced hypoalbuminemia in sepsis.
Wang
Xin-Ying
XY
Research Institute of General Surgery, Jinling Hospital, Nanjing 210002, China. wxinying@263.net
Li
Wei-Qin
WQ
Lu
Jun
J
Li
Ning
N
Li
Jie-Shou
JS
D000418:Albumins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D011498:Protein Precursors / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D008070:Lipopolysaccharides; D011498:Protein Precursors; D012333:RNA, Messenger