NF-κB protects human neuroblastoma cells from nitric oxide-induced apoptosis through upregulating biglycan.

Excessive nitric oxide (NO) produced in inflammation may result in oxidative stress, which is closely related to the neurodegenerative diseases and brain damage. Massive NO production can enhance NF-κB activity in various neural cells, but the function of this activation by NO and the target genes transactivated by NF-κB are still largely unknown. In the present study, our results showed sodium nitropruside (SNP), a NO donor, triggered apoptotic cell death and NF-κB activation in human neuroblastoma SH-EP1 cells, and inhibition of NF-κB activation by its super endogenous inhibitor, I-κBαM, sensitized SH-EP1 cells to NO-induced apoptosis. Conversely, NF-κB activation induced by insulin-like growth factor (IGF)-1 antagonizes NO-induced apoptotic cell death in SH-EP1 cells. In addition, cDNA microarray analysis showed biglycan, an extracellular glycoprotein, was up-regulated by NF-κB, and recombinant biglycan protein conferred a protective effect on NF-κB mediated NO-induced apoptotic cell death in SH-EP1 cells. These findings suggest biglycan may serve as a potential target in preventing NO-induced neurodegenerative diseases.