INDUCTION OF HEME OXYGENASE IS A RAPID, PROTECTIVE RESPONSE IN RHABDOMYOLYSIS IN THE RAT
INDUCTION OF HEME OXYGENASE IS A RAPID, PROTECTIVE RESPONSE IN RHABDOMYOLYSIS IN THE RAT
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DOI：
10.1172/jci115847
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发表时间：
1992-07-01
影响因子：
15.9
通讯作者：
ROSENBERG, ME
中科院分区：
文献类型：
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作者：
NATH, KA;BALLA, G;ROSENBERG, ME
血红素蛋白，如肌红蛋白或血红蛋白，当释放到细胞外空间时，可能会引发组织毒性。肌红蛋白直接参与横纹肌溶解性肾功能衰竭的发病机制。在这种综合征的甘油模型中，我们证明肾脏通过诱导血红素降解酶、血红素加氧酶以及增加铁的主要细胞储存库铁蛋白的合成来对这种过多的血红素蛋白做出反应。预先预先注射一次血红蛋白可预防肾衰竭并显著降低死亡率(从100%降至14%)。相反，用竞争性的血红素加氧酶抑制剂消除这种反应会加剧肾功能障碍。我们提供了第一个体内证据，证明诱导血红素加氧酶与铁蛋白的合成是一种快速的、保护性的抗氧化反应。我们的发现为横纹肌溶解的高危人群提供了一种治疗策略。
Heme proteins such as myoglobin or hemoglobin, when released into the extracellular space, can instigate tissue toxicity. Myoglobin is directly implicated in the pathogenesis of renal failure in rhabdomyolysis. In the glycerol model of this syndrome, we demonstrate that the kidney responds to such inordinate amounts of heme proteins by inducing the heme-degradative enzyme, heme oxygenase, as well as increasing the synthesis of ferritin, the major cellular repository for iron. Prior recruitment of this response with a single preinfusion of hemoglobin prevents kidney failure and drastically reduces mortality (from 100% to 14%). Conversely, ablating this response with a competitive inhibitor of heme oxygenase exacerbates kidney dysfunction. We provide the first in vivo evidence that induction of heme oxygenase coupled to ferritin synthesis is a rapid, protective antioxidant response. Our findings suggest a therapeutic strategy for populations at a high risk for rhabdomyolysis.