Hmox-1 constitutes an adaptive response to effect antioxidant cardioprotection - A study with transgenic mice heterozygous for targeted disruption of the heme oxygenase-1 gene

Article

关键词: HUMAN SKIN FIBROBLASTS;    OXIDATIVE STRESS;    ISCHEMIA-REPERFUSION;    INDUCTION;    HEART;    2ND-MESSENGER;    EXPRESSION;    FERRITIN;    INJURY;    CELLS;   

DOI  :  10.1161/01.CIR.103.12.1695

来源: SCIE

【 摘 要 】

Background--Heme oxygenase-1 (Hmox-1) has been implicated in protection of cells against ischemia/reperfusion injury. Methods and Results-To examine the physiological role of Hmox-1, a line of heterozygous Hmox-1-knockout mice was developed by targeted disruption of the mouse Hmox-1 gene. Transgene integration was confirmed and characterized at the protein level A 40% reduction of Hmox-1 protein occurred in the hearts of H-mox-1(+/-) mice compared with those of wild-type mice. Isolated mouse hearts from H-mox-1(+/-) mice and wild-type controls perfused via the Langendorff mode were subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion. The H-mox-1(+/-) hearts displayed reduced ventricular recovery, increased creatine kinase release, and increased infarct size compared with those of wild-type controls, indicating that these H-mox-1(+/-) hearts were more susceptible to ischemia/reperfusion injury than wild-type controls. These results also suggest that H-mox-1(+/-) hearts are subjected to increased amounts of oxidative stress. Treatment with 2 different antioxidants, Trolox or N-acetylcysteine, only partially rescued the H-mox-1(+/-) hearts from ischemia/reperfusion injury. Preconditioning, which renders the heart tolerant to subsequent lethal ischemia/reperfusion, failed to adapt the hearts of the H-mox-1(+/-) mice compared with wild-type hearts. Conclusions These results demonstrate that Hmox-1 plays a crucial role in ischemia/reperfusion injury not only by functioning as an intracellular antioxidant but also by inducing its own expression under stressful. conditions such as preconditioning.

【 授权许可】

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