HEME OXYGENASE 1 PROTECTS AGAINST HEPATIC HYPOXIA AND INJURY FROM HEMORRHAGE VIA REGULATION OF CELLULAR RESPIRATION

被引：31

作者：

Vallabhaneni, Raghuveer ^{[1
]}

Kaczorowski, David J. ^{[1
]}

Yaakovian, Michael D. ^{[1
]}

Rao, Jayashree ^{[1
]}

Zuckerbraun, Brian S. ^{[1
,2
]}

机构：

[1] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA

[2] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA

来源：

SHOCK | 2010年 / 33卷 / 03期

关键词：

Heme oxygenase; carbon monoxide; hemorrhage; hypoxia; hepatocytes; liver; respiration; CARBON-MONOXIDE; NITRIC-OXIDE; RAT-LIVER; EXPRESSION PATTERN; GENE-TRANSFER; SHOCK; ACTIVATION; STRESS; RESUSCITATION; INHIBITION;

D O I：

10.1097/SHK.0b013e3181b0f566

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

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.

引用

页码：274 / 281

页数：8

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