Protective effects of lipopolysaccharide preconditioning against nitric oxide neurotoxicity

✍ Scribed by Chia-Yen Huang; Hui-I Yang; Shang-Der Chen; Fu-Zen Shaw; Ding-I Yang

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 858 KB
• Volume: 86
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.21594

✦ Synopsis

Abstract

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. © 2007 Wiley‐Liss, Inc.