Carbon monoxide mediates heme oxygenase 1 induction via Nrf2 activation in hepatoma cells
Carbon monoxide mediates heme oxygenase 1 induction via Nrf2 activation in hepatoma cells
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DOI：
10.1016/j.bbrc.2006.03.058
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发表时间：
2006-05-12
影响因子：
3.1
通讯作者：
Chung, HT
中科院分区：
文献类型：
--
作者：
Lee, BS;Heo, J;Chung, HT
一氧化碳(CO)和一氧化氮(NO)是两种气体分子，对多种细胞类型的氧化应激和炎症反应具有细胞保护作用。目前已知，一氧化氮合酶(NOS)产生的NO诱导血红素氧合酶1(HO1)的表达，HO1产生的CO抑制诱导型NOS的表达。这里..。我们首先展示了CO介导的HO1在人肝细胞中的诱导及其可能的机制。将HepG2细胞或原代肝细胞暴露于CO可显著诱导HO1的产生，且呈剂量和时间依赖关系。CO介导的HO1诱导可被MAPKs阻断，但不受PI3和NF-kappaB抑制剂的影响。此外，CO诱导Nrf2的核转位和积聚，而MAPKs抑制剂可抑制这一作用。综上所述，我们认为CO通过MAPKs信号通路诱导Nrf2激活，从而导致HepG2细胞HO1的表达。(C)2006 Elsevier Inc.保留所有权利。
Carbon monoxide (CO) and nitric oxide (NO) are two gas molecules which have cytoprotective functions against oxidative stress and inflammatory responses in many cell types. Currently, it is known that NO produced by nitric oxide synthase (NOS) induces heme oxygenase 1 (HO1) expression and CO produced by the HO1 inhibits inducible NOS expression. Here.. we first show CO-mediated HO1 induction and its possible mechanism in human hepatocytes. Exposure of HepG2 cells or primary hepatocytes to CO resulted in dramatic induction of HO1 in dose- and time-dependent manner. The CO-mediated HO1 induction was abolished by MAP kinase inhibitors (MAPKs) but not affected by inhibitors of PI3 kinase or NF-kappa B. In addition, CO induced the nuclear translocation and accumulation of Nrf2, which suppressed by MAPKs inhibitors. Taken together, we suggest that CO induces Nrf2 activation via MAPKs signaling pathways, thereby resulting in HO1 expression in HepG2 cells. (c) 2006 Elsevier Inc. All rights reserved.