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Publication : A key role for heme oxygenase-1 in nitric oxide resistance in murine motor neurons and glia.

First Author  Bishop A Year  2004
Journal  Biochem Biophys Res Commun Volume  325
Issue  1 Pages  3-9
PubMed ID  15522193 Mgi Jnum  J:93524
Mgi Id  MGI:3057234 Doi  10.1016/j.bbrc.2004.10.010
Citation  Bishop A, et al. (2004) A key role for heme oxygenase-1 in nitric oxide resistance in murine motor neurons and glia. Biochem Biophys Res Commun 325(1):3-9
abstractText  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.
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