PREVENTION OF HYPOXIC LIVER-CELL NECROSIS BY IN-VIVO HUMAN BCL-2 GENETRANSFECTION

Prevention of hypoxic cell death is a key to successful liver transpla ntation. We developed a new method for preventing liver hypoxic cell d eath by introducing an anti-cell death gene directly into rat livers. When the human bcl-2 gene (hbcl-2) was directly transfected into rat l ivers together with nonhistone chromosomal protein high mobility group 1 (HMG1) by the hemagglutinating virus of Japan (Sendai virus; HVJ) - liposome method, human Bcl-2 protein (hBcl-2) was efficiently expresse d. Electron microscopy and fluorescence microscopy revealed that hepat ocytes expressing exogenous hBcl-2 were almost completely protected th e hypoxic cell necrosis. The expression of the hBcl-2 also inhibited a ctivation of caspase-3 (-like) proteases and liver dysfunction. Thus, we conclude that transfection of the hbcl-2 gene through HVJ-liposome method is useful to prevent liver cell necrosis induced by hypoxia. Th is finding could lead to new strategies to avoid the hypoxic cell deat h, the major problem in liver transplantation. (C) 1998 Academic Press .