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v9.9.1 along with 75 versions of bible[FullDownload].rarHeme Oxygenase-1 Mediates In Vitro Detoxification of Nitric Oxide: A Possible Mechanism of Iron-Induced Pulmonary Injury?

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Pulmonary injury is a frequent complication of iron overload. Recent evidence suggests that oxidative stress is implicated in the pathogenesis of pulmonary injury. Thus, the present study aimed to determine whether heme oxygenase-1 (HO-1), an important antioxidant enzyme, is induced by iron and involved in iron-induced pulmonary injury. The influence of hemin (a HO-1 inducer) and Zn protoporphyrin (ZnP, a HO-1 inhibitor) on iron-induced cell injury was determined in human pulmonary microvascular endothelial cells and the underlying molecular mechanisms were explored. We found that hemin induced, whereas ZnP inhibited, HO-1 expression and function in human pulmonary microvascular endothelial cells. The protective effects of hemin on cell injury induced by iron were completely abolished by HO-1 antisense oligonucleotides. Moreover, hemin upregulated nuclear factor-E2-related factor 2 (Nrf2) and regulated the nuclear translocation of Nrf2 via the mitogen-activated protein kinases (MAPKs) pathway. Importantly, pretreatment with hemin attenuated iron-induced ROS production and p38, but not extracellular signal-regulated kinase (ERK)1/2, activation. HO-1 expression induced by hemin was mediated through p
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