Expression of Bcl-2 family reduces apoptotic hepatocytes after excessive hepatectomy.
Excessive hepatectomy often causes fatal hepatic failure, but the mechanism is unknown. We used a novel protocol of partial 90 and 95% hepatectomy (PHx) to investigate this mechanism in 2 groups of rats. The 90% PHx rats survived, but the 95% PHx animals died of hepatic failure. In the latter, cytokine (interleukin-6, tumor necrosis factor-alpha) levels and the apoptotic hepatocyte count increased, and there were few mitotic cells. By contrast, in the 90% PHx rats, the mitotic cell count increased, and more anti-apoptotic Bcl-xL protein was expressed. These results demonstrate that expression of Bcl-xL protein as an anti-apoptotic factor or regeneration factor contributes to survival after 90% PHx. Using an adenovirus vector, the human bcl-2 gene (hbcl-2) was therefore transfected to DA rat livers where it was efficiently expressed, and then 95% PHx was performed. Liver damage was decreased and the apoptotic cell count decreased too, but the rats died. We concluded that transfection of the hbcl-2 gene partly prevents cytotoxicity (apoptosis), but cannot ensure survival. Thus, some other factor is required (e.g., a regeneration stimulator) to maintain life in these models.
Kamimukai
N
N
Department of Surgery II, Yokohama City University School of Medicine, Yokohama, Japan. nokami@urahp.yokohama-cu.ac.jp
Togo
S
S
Hasegawa
S
S
Kubota
T
T
Kurosawa
H
H
Li
X K
XK
Suzuki
S
S
Shimada
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D016207:Cytokines / Q000097:blood; D015870:Gene Expression / Q000502:physiology*; D019254:Genes, bcl-2 / Q000502:physiology*; D006498:Hepatectomy / Q000379:methods*; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D011184:Postoperative Period; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D016019:Survival Analysis; D014162:Transfection; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C494813:Bcl2l1 protein, rat; D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein