[Potential mechanism underlying down-regulation of albumin expression induced by lipopolysaccharide in rat hepatocytes].
OBJECTIVE
To investigate the potential molecular mechanism underlying down-regulation of albumin expression induced by lipopolysaccharide (LPS) in rat hepatocytes.


METHODS
The albumin mRNA expression and albumin protein levels in the supernatant were observed at 0, 2, 8, 12 and 24 hours after 1 micro g/ml LPS treatment. The albumin mRNA expression was determined by RT-PCR, and albumin protein levels were assayed with EIA in the supernatant of hepatocytes pretreated with specific inhibitors of extracellular signal-regulated kinase (PD98059) and p38 kinase (SB203580).


RESULTS
The albumin mRNA expression was reduced to 70% of baseline value, meanwhile, the albumin protein concentration in the supernatant was reduced by 50% compared with the controls after 24 hours of LPS treatment. Pretreatment with PD98059 and SB203580 did significantly inhibit the reduction of albumin by LPS at the given dose.


CONCLUSIONS
The results indicate that LPS can induce the reduction of albumin synthesis by down-regulation of albumin mRNA expression at transcription level, and the process may be related to the signal transducation of extracellular signal-regulated kinase and p38 kinase.
Wang
Xin-ying
XY
Research Institute of General Surgery, Jinling Hospital, Nanjing 210002, China.
Li
Ning
N
Li
Wei-qin
WQ
Li
Jie-shou
JS
D000418:Albumins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005419:Flavonoids / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D000418:Albumins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D008070:Lipopolysaccharides; D011725:Pyridines; D012333:RNA, Messenger; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one