Protective effect of adeno-mediated human Bcl-xL gene transfer to the mouse liver in a partial ischemia/reperfusion model.
BACKGROUND
The protective effect of heat preconditioning has been ascribed to the induction of heat shock proteins (HSP) in the liver. We detected an increase in Bcl-xL expression prior to HSP 70 expression in the rat liver after heat preconditioning. The net effect of overexpression of human Bcl-xL with a recombinant adenovector was estimated in a partial ischemia/reperfusion model of the mouse liver.


METHODS
The time courses of the expression of HSP, Bcl-xL, Bcl-2, Bax, and Bag-1 in the SD rat liver after heat preconditioning were studied by Western blotting. The localizations of Bcl-xL, Bcl-2, and Bax at 6 h after preconditioning were examined by immunostaining. The expression of Bcl-xL in the C57/BL mouse liver after intravenous injection of the recombinant adenovector was assessed by Western blotting and immunostaining. The protective effect of overexpression of Bcl-xL was estimated in a 60-min partial ischemia/reperfusion model of the mouse liver.


RESULTS
The expression of Bcl-xL peaked 12 h after heat preconditioning. The overexpression of Bcl-xL decreased enzyme release, histological cell injury, and the number of TUNEL-positive cells.


CONCLUSIONS
Transfer of the human Bcl-xL gene to the liver had a protective effect against ischemia/reperfusion injury in a mouse model.
Honda
Kazuo
K
Department of Organ Regulatory Surgery, Ehime Graduate School of Medicine, Japan. honkazu@m.ehime-u.ac.jp
Tohyama
Taiji
T
Kotegawa
Hiroshi
H
Kojima
Yoh
Y
Kushihata
Fumiki
F
Watanabe
Jota
J
Kobayashi
Nobuaki
N
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018197:Hepatoblastoma; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051020:bcl-X Protein / Q000235:genetics* / Q000378:metabolism
C494811:BCL2L1 protein, human; D018840:HSP70 Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein