Heme oxygenase 1 protects against hepatic hypoxia and injury from hemorrhage via regulation of cellular respiration.
Heme oxygenase 1 (HO-1) is an important regulator of the cellular response to stress and inflammation. These investigations test the hypothesis that HO-1 overexpression protects against hemorrhage-induced hypoxia by regulating cellular respiration and oxygen availability. Male C57BL/6 mice or primary mouse hepatocytes were treated with adenoviral gene transfer of HO-1 (AdHO-1) or beta-galactosidase (AdLacZ). Mice were subjected to hemorrhagic shock and resuscitation or cannulation without hemorrhage. AdHO-1 prevented hemorrhagic shock/resuscitation-induced liver injury. In addition, AdHO-1 prevented hemorrhage-induced liver hypoxia and depletion of adenosine triphosphate. In vitro, HO-1 overexpression resulted in decreased cellular respiration under hypoxic conditions as determined by oxygen consumption and cytochrome c oxidase activity. This resulted in increased intracellular oxygen levels in the setting of low oxygen tensions. In conclusion, HO-1 overexpression protects the liver against hemorrhage-induced injury. This may be secondary to the ability of HO-1 to protect against bioenergetic failure via regulation of cellular respiration.
Vallabhaneni
Raghuveer
R
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburg, PA, USA.
Kaczorowski
David J
DJ
Yaakovian
Michael D
MD
Rao
Jayashree
J
Zuckerbraun
Brian S
BS
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006470:Hemorrhage / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D000860:Hypoxia / Q000517:prevention & control*; D008099:Liver / Q000293:injuries*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010101:Oxygen Consumption; D012771:Shock, Hemorrhagic / Q000517:prevention & control*
D051547:Heme Oxygenase-1