A key role for heme oxygenase-1 in nitric oxide resistance in murine motor neurons and glia
A key role for heme oxygenase-1 in nitric oxide resistance in murine motor neurons and glia
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DOI：
10.1016/j.bbrc.2004.10.010
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发表时间：
2004-12-03
影响因子：
3.1
通讯作者：
Demple, B
中科院分区：
文献类型：
--
作者：
Bishop, A;Yet, SF;Demple, B
一氧化氮在低水平下用于细胞间信号传导，在高水平下用作炎症期间的细胞毒性武器。细胞NO抗性可以通过预先暴露于亚致死NO水平以诱导防御基因表达（适应性NO抗性）来增加，这与血红素加氧酶-1（HO 1）的表达增加相关，并且被血红素加氧酶抑制剂阻断。然而，其他活动仍有可能受到抑制剂的影响。为了解决这个问题，我们对HO 1的作用进行了遗传研究。我们在这里表明，原代培养的脊髓运动神经元和神经胶质细胞从纯合子HO 1-null小鼠显着更敏感的NO细胞毒性比细胞表达HO 1。暴露于NO后，HO 1缺陷细胞比具有一个或两个功能性HO 1基因拷贝的HO 1表达细胞更容易发生凋亡。这些结果证实了HO 1在神经元细胞中作为对抗NO毒性的前线防御的体内作用。(C)2004年爱思唯尔公司All rights reserved.
Nitric oxide is utilized at low levels for intercellular signaling, and at high levels as a cytotoxic weapon during inflammation. Cellular NO resistance can be increased by prior exposure to sublethal NO levels to induce defense gene expression (adaptive NO resistance), which has been correlated with increased expression of heme oxygenase-1 (HO1) and was blocked by a heme oxygenase inhibitor. However, the possibility remained that other activities were affected by the inhibitor. To address this question, we conducted a genetic study of the HO1 role. We show here that primary cultures of spinal motor neurons and glia from homozygous HO1-null mice are strikingly more sensitive to NO cytotoxicity than are cells expressing HO1. Following an exposure to NO, the HO1-deficient cells were much more prone to apoptosis than were HO1-expressing cells with either one or two copies of a functional HO1 gene. These results confirm the in vivo role of HO1 as a front-line defense against NO toxicity in neuronal cells. (C) 2004 Elsevier Inc. All rights reserved.