Messenger RNA profiles in liver injury and stress: a comparison of lethal and nonlethal rat models.
Liver damage activates processes aimed at repairing damage; simultaneously, liver functions required for survival must be maintained. The expression of genes responsible for both in rat models of lethal (lipopolysaccharide, 90% hepatectomy, and d-galactosamine) and nonlethal (turpentine, 70% hepatectomy, and acetaminophen) liver damage and stress was measured at 3, 6, 12, and 24 h after the intervention and quantitated as the area between the control curves and the test curves (AUC). The expression of genes for cell division and remodeling was upregulated most in the lethal models. The expression of most liver-specific function genes was reduced. Positive AUC was found for ARG, ASL, CPT1, Mdr1b, Mdr2, and PEPCK. It is concluded that a high expression of genes for repair of liver damage is associated with reduced expression of genes for several liver-specific functions, possibly reflecting a limited capacity for transcriptional activity. Maintained or increased expression of selected function genes indicates that the corresponding functions have high priority. The liver sustains metabolic homeostasis ensuring that other organs in the body function normally. Simultaneously, the processes required for the integrity of its own structure and function are maintained as a result of regulated expression of the genes that produce the proteins needed to perform both set of functions.
Tygstrup
Niels
N
Liver Unit, Laboratory of Hepatology, Rigshospitalet 2151, 9 Blegdamsvej, DK 2100 Copenhagen, Denmark. tygstrup@rh.dk
Bangert
Kristian
K
Ott
Peter
P
Bisgaard
Hanne Cathrine
HC
D000082:Acetaminophen / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005688:Galactosamine / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism; D007509:Irritants; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000293:injuries* / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D013997:Time Factors; D014158:Transcription, Genetic; D014425:Turpentine
D018712:Analgesics, Non-Narcotic; D018076:DNA, Complementary; D007509:Irritants; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D000082:Acetaminophen; D005688:Galactosamine; D014425:Turpentine