Overexpression of heme oxygenase protects renal tubular cells against cold storage injury - Studies using hemin induction and HO-1 gene transfer
Overexpression of heme oxygenase protects renal tubular cells against cold storage injury - Studies using hemin induction and HO-1 gene transfer
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DOI：
10.1097/00007890-200111150-00005
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发表时间：
2001-11-15
期刊：
影响因子：
6.2
通讯作者：
Salahudeen, AK
中科院分区：
文献类型：
--
作者：
Salahudeen, AA;Jenkins, JK;Salahudeen, AK
血红素加氧酶-1（HO-1）是一种分子量为32 kd的微粒体酶，是机体对多种伤害性刺激的适应性反应。我们研究了HO-1在肾近端肾小管上皮细胞（RPTE）冷藏中的可能作用。血红素，一种有效的HO-1诱导剂，引起HO-1 mRNA和蛋白表达的时间依赖性增加。氯化血红素预处理人RPTE细胞冷藏前赋予细胞保护作用。HO-1蛋白的增加与催化活性铁的快速和早期增加以及细胞铁蛋白的强劲增加有关。去铁胺，铁螯合抗氧化剂，防止氯化血红素诱导的铁释放和铁蛋白的增加，这表明铁释放作为铁蛋白诱导的先决机制。为了验证氯化血红素细胞保护作用的近因是由于HO-1诱导，我们在冷藏前用HO-1表达载体瞬时转染LL-CPK 1猪肾细胞。HO-1基因转染可增加HO-1蛋白表达，减少细胞在冷藏过程中的损伤。先前诱导HO-1可预防冷储存诱导的细胞损伤的新观察表明，类似的策略可能证明在移植期间有效预防冷储存诱导的器官损伤。
Heme oxygenase-1 (HO-1), a 32-kd microsomal enzyme, is induced as an adaptive response to a wide variety of injurious stimuli. We examined the possible role of HO-1 in cold storage of renal proximal tubular epithelial (RPTE) cells. Hemin, a potent HO-1-inducer, caused a time-dependent increase in HO-1 mRNA and protein expression. Hemin pretreatment of human RPTE cells before cold storage conferred cytoprotection. Increased HO-1 protein was associated with a brisk and early increase in catalytically active iron and a robust increase in cellular ferritin. Deferoxamine, an iron sequestrating antioxidant, prevented hemin-induced iron release and the increase in ferritin, suggesting iron release as an antecedent mechanism for ferritin induction. To verify that the proximate cause of hemin cytoprotection was due to HO-1 induction, we transiently transfected LL-CPK1 porcine kidney cells with a HO-1 expression vector before cold storage. HO-1 transfection resulted in increased expression of HO-1 protein and reduced cell injury during cold storage. The novel observation that prior induction of HO-1 prevents cold storage-induced cell injury suggests that a similar strategy may prove efficacious in preventing cold storage-induced organ damage during transplantation.