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Protective effects of lipopolysaccharide preconditioning against nitric oxide neurotoxicity


, : Protective effects of lipopolysaccharide preconditioning against nitric oxide neurotoxicity. Journal of Neuroscience Research 86(6): 1277-1289

We have characterized lipopolysaccharide (LPS) preconditioning-induced neuroprotective mechanisms against nitric oxide (NO) toxicity. Pretreatment of rat cortical cultures with LPS attenuated neurotoxicity of NO donors, including sodium nitroprusside (SNP) and diethylamine NONOate (NONOate). A transiently increased expression of endothelial nitric oxide synthase (eNOS) accompanied by an increase in NO production was observed during LPS preconditioning. Application of NOS inhibitors including L-N(5)-(1-iminoethyl)-ornithine (L-NIO) and L-nitroarginine methylester (L-NAME) abolished LPS-dependent protection against SNP toxicity. The LPS effect was also blocked by KT5823, an inhibitor of cGMP-dependent protein kinase (PKG). Consistently, application of 8-bromo-cyclic GMP (8-Br-cGMP), a slowly degradable cGMP analogue capable of PKG activation, was neuroprotective. LPS preconditioning resulted in a heightened neuronal expression of Bcl-2 protein that was abolished by L-NAME and KT5823, the respective inhibitors of NOS and PKG. Together, our results reveal the signaling cascade of "LPS -> eNOS -> NO -> cGMP/ PKG -> Bcl-2" that might have contributed to the LPS protective effects in cortical neurons. (C) 2007 Wiley-Liss, Inc.

US$19.90

PMID: 18092358

DOI: 10.1002/jnr.21594


Other references

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