HEMOGLOBIN PROVIDES PROTECTION AGAINST LETHAL ENDOTOXEMIA IN RATS - THE ROLE OF HEME OXYGENASE-1

被引：282

作者：

OTTERBEIN, L

SYLVESTER, SL

CHOI, AMK

机构：

[1] JOHNS HOPKINS UNIV,SCH MED,DIV PULM & CRIT CARE,BALTIMORE,MD 21205

[2] SCIOS NOVA PHARMACEUT INC,BALTIMORE,MD

来源：

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY | 1995年 / 13卷 / 05期

关键词：

D O I：

10.1165/ajrcmb.13.5.7576696

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Heme oxygenase (HO) catalyzes the rate-limiting step in the degradation of heme to bilirubin, HO-1 is highly induced by heme, its major substrate, and nonheme products, including metal ions and hormones. Interest in HO-1 has been stimulated recently by observations that HO-1 is also highly induced in response to oxidative stress in vitro, The physiologic significance of HO-1 induction following oxidant injury in vivo, however, is poorly understood. In a rat model of lipopolysaccharide endotoxin (LPS)-induced lung injury and sepsis, we demonstrate that the lung responds to LPS by expressing high levels of HO-1 mRNA and enzyme activity. We hypothesize that this HO-1 induction could play a critical role in the lung's defense against LPS. Pretreatment of rats with hemoglobin, a potent inducer of HO-1, resulted in HO-1 induction and more importantly provided complete protection against subsequent lethal endotoxemia (100% survival). Tin protoporphyrin, a competitive inhibitor of HO, blocked this protective effect of hemoglobin and rendered the rats more susceptible to a lethal dose of LPS, Taken together, these data strongly implicate HO-1 in playing an important role in the defense against endotoxic shock, with potential therapeutic implications.

引用

页码：595 / 601

页数：7

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