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. MATERIAL AND 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. CONCLUSION: 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.
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. MATERIAL AND METHODS: After infecting Hep3B and rodent livers with adenovirus carrying CMV promoter sequences linked to the humanmyoglobin 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. CONCLUSION: 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.
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Authors: Adil A Khan; Yaoming Wang; Yunjuan Sun; Xiao Ou Mao; Lin Xie; Erin Miles; Justin Graboski; Sylvia Chen; Lisa M Ellerby; Kunlin Jin; David A Greenberg Journal: Proc Natl Acad Sci U S A Date: 2006-11-10 Impact factor: 11.205
Authors: G Kristiansen; M Rose; C Geisler; F R Fritzsche; J Gerhardt; C Lüke; A-M Ladhoff; R Knüchel; M Dietel; H Moch; Z Varga; J-P Theurillat; T A Gorr; E Dahl Journal: Br J Cancer Date: 2010-06-08 Impact factor: 7.640
Authors: Jane Fraser; Luciane Vieira de Mello; Deborah Ward; Huw H Rees; Daryl R Williams; Yongxiang Fang; Yongchang Fang; Andrew Brass; Andrew Y Gracey; Andrew R Cossins Journal: Proc Natl Acad Sci U S A Date: 2006-02-09 Impact factor: 11.205
Authors: H J Abu-Toamih Atamni; G Kontogianni; I Binenbaum; R Mott; H Himmelbauer; H Lehrach; A Chatziioannou; Fuad A Iraqi Journal: Mamm Genome Date: 2019-10-24 Impact factor: 2.957