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Prevention of Hypoxic Liver Cell Necrosis byin VivoHumanbcl-2Gene Transfection

1998; Elsevier BV; Volume: 243; Issue: 1 Linguagem: Inglês

10.1006/bbrc.1997.7925

1090-2104

Kazuo Yamabe, Shigeomi Shimizu, Wataru Kamiike, Satoshi Waguri, Yutaka Eguchi, Junichi Hasegawa, S. Okuno, Yasuhiko Yoshioka, Toshinori Ito, Yoshiki Sawa, Yasuo Uchiyama, Yoshihide Tsujimoto, Hikaru Matsuda,

Endoplasmic Reticulum Stress and Disease

Prevention of hypoxic cell death is a key to successful liver transplantation. We developed a new method for preventing liver hypoxic cell death by introducing an anti-cell death gene directly into rat livers. When the human bcl-2 gene (hbcl-2) was directly transfected into rat livers together with non-histone 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 expressed. Electron microscopy and fluorescence microscopy revealed that hepatocytes expressing exogenous hBcl-2 were almost completely protected the hypoxic cell necrosis. The expression of the hBcl-2 also inhibited activation 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. This finding could lead to new strategies to avoid the hypoxic cell death, the major problem in liver transplantation.