Myoglobin gene expression attenuates hepatic ischemia reperfusion injury.
BACKGROUND
Cellular functions are maintained by a continuous supply of ATP, which is supplied efficiently by mitochondrial oxidative phosphorylation. Since myoglobin, found in cardiac myocytes and red skeletal muscle, but not in the liver, facilitates oxygen diffusion under low oxygen conditions and enhances oxidative phosphorylation, this study seeks to enhance hepatic ATP levels and attenuate ischemia-reperfusion injury in rodent livers by adenovirus-mediated myoglobin expression.


METHODS
After infecting Hep3B and rodent livers with adenovirus carrying CMV promoter sequences linked to the human myoglobin gene (AdCMVMyo), reverse transcriptase-PCR and immunodetection for myoglobin, and cellular and hepatic ATP levels were examined. The effect of myoglobin was evaluated in a hepatic ischemia-reperfusion model in the rat.


RESULTS
Myoglobin expression was confirmed in Hep3B and rat livers after AdCMVMyo infection. The ATP levels in Hep3B cells and C57BL/6 mice livers 72 h after AdCMVMyo transfection were significantly higher than control levels and those after adenovirus-mediated beta-galactosidase transfection. Finally, expression of myoglobin attenuated ischemia-reperfusion injury in the rat liver.


CONCLUSIONS
These results indicate that myoglobin gene transfer to the liver enhanced ATP levels both in vitro and in vivo and might be a novel strategy to reduce ischemia-reperfusion injury.
Nitta
Takashi
T
Department of Gastroenterological Surgery, Kyoto University, Graduate School of Medicine, 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto, 606-8507 Japan.
Xundi
Xu
X
Hatano
Etsuro
E
Yamamoto
Naritaka
N
Uehara
Tetsuya
T
Yoshida
Masanori
M
Harada
Nobuko
N
Honda
Kazuo
K
Tanaka
Akira
A
Sosnowski
Donna
D
Chance
Britton
B
Yamaoka
Yoshio
Y
D000255:Adenosine Triphosphate / Q000378:metabolism; D000256:Adenoviridae; D000818:Animals; D002460:Cell Line; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D008099:Liver / Q000098:blood supply* / Q000378:metabolism*; D008297:Male; D051379:Mice; D023421:Models, Animal; D009211:Myoglobin / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control / Q000628:therapy*; D014162:Transfection
D009211:Myoglobin; D000255:Adenosine Triphosphate