Hemagglutinating virus of Japan-artificial viral envelope liposome-mediated cotransfer of bag-1 and bcl-2 genes protects hepatic cells against ischemic injury through BAG-1-assisted preferential enhancement of bcl-2 protein expression.
Hepatic injury subsequent to ischemia-reperfusion (I/R) was demonstrated in our previous study to be prevented by hemagglutinating virus of Japan (HVJ)-artificial viral envelope (AVE) liposome-mediated gene transfer of the antiapoptotic gene, human bcl-2 (h-bcl-2). In the present study, we introduced simultaneously both mouse Bcl-2-associated athanogene 1 (m-bag-1) and the h-bcl-2 gene by the same HVJ-AVE liposome transfection method, and found that I/R-induced hepatic injuries such as release of hepatic marker enzymes into blood, cell morphological degeneration, and cellular DNA strand cleavage were suppressed more effectively than by transfection with either gene singly. In addition, the h-Bcl-2 expression level in the ischemic state, but not in the nonischemic state, was markedly higher in h-bcl-2/m-bag-1-cotransfected liver than in h-bcl-2-transfected liver. In contrast, the m-BAG-1 expression level in the ischemic state, but not in the nonischemic state, was only slightly higher in h-bcl-2/m-bag-1-cotransfected liver than in m-bag-1-transfected liver. Thus, with dual gene cotransfer, coexistent Bcl-2 protein exerts no activity to assist a marked enhancement of BAG-1 protein, whereas the function of overexpressed BAG-1 as a Bcl-2-binding protein may lead to the enhancement of efficient expression of h-Bcl-2 in I/R-treated liver as compared with nonischemic liver, which results in repression of diverse I/R-induced cell death symptoms, presumably through the formation of functional complexes of BAG-1 and Bcl-2.
Yanada
Shinobu
S
Laboratory of Cell Death Control BioTechnology, Hiroshima Prefectural University School of BioSciences, Shobara, Hiroshima 727-0023, Japan.
Sasaki
Masao
M
Takayama
Shinichi
S
Kaneda
Yasufumi
Y
Miwa
Nobuhiko
N
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D018014:Gene Transfer Techniques; D019254:Genes, bcl-2; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008081:Liposomes; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D029082:Sendai virus / Q000235:genetics*; D014157:Transcription Factors
C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008081:Liposomes; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors