Expression of Bcl-2 family reduces apoptotic hepatocytes after excessive hepatectomy

European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
Nobuyuki KamimukaiHiroshi Shimada

Abstract

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.

Citations

May 27, 2005·The Journal of Surgical Research·Hirochika MakinoHiroshi Shimada
Jun 24, 2006·Annals of Surgery·Nodir MadrahimovUta Dahmen
Jun 15, 2007·Journal of Gastroenterology and Hepatology·Naomasa YoshidaHirofumi Takemura
Jul 5, 2013·PLoS Biology·So Hee DhoSteven J Weintraub
Feb 18, 2011·The Journal of Surgical Research·Hironobu AmanoKatsutoshi Yoshizato
May 7, 2010·The Journal of Surgical Research·Hirochika MakinoYoshihide Hayashizaki
Jul 28, 2007·The Journal of Surgical Research·Kazuteru WatanabeHiroshi Shimada
Jan 21, 2009·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Atsushi IshibeHiroshi Shimada

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