Interactions among nitric oxide and Bcl-family proteins after MPP+ exposure of SH-SY5Y neural cells II: Exogenous NO replicates MPP+ actions

✍ Scribed by Jameel Dennis; James P. Bennett Jr.

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 497 KB
• Volume: 72
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.10540

✦ Synopsis

Abstract

In the preceding companion article, we showed that the neurotoxin methylpyridinium (MPP^+^) increases mitochondrial nitric oxide (NO), causes a post‐transcriptional, NO‐dependent increase in Bax protein and produces caspase‐dependent apoptosis and caspase‐independent cell death. In the present study, we show that exogenous NO replicates these findings. The long‐term NO generator diethylenetriamine‐NO (DETA‐NO) reproduced the post‐transcriptional Bax protein increase, but did not increase Bcl‐2 or Bcl‐X~L~ proteins. Like MPP^+^, DETA‐NO caused an early decrease in Bcl‐2 mRNA, did not increase Bax protein in ρ^0^ cells and caused caspase‐ and cycloheximide‐dependent apoptosis and caspase‐independent cell death. We developed cell lines with inducible overexpression of Bcl proteins, at levels relevant to those we found in cells exposed to MPP^+^ or DETA‐NO. Inducible overexpression (∼2‐fold) of Bcl‐2 or Bcl‐X~L~ proteins reduced MPP^+^ or NO‐induced apoptosis but did not affect cell death. Inducible Bax overexpression (∼5‐fold) slightly increased cell death. Our results show that exogenous NO mimics actions of MPP^+^ on SH‐SY5Y neuroblastoma cells and supports the mediation of MPP^+^ neurotoxicity by NO generated intracellularly in mitochondria. © 2003 Wiley‐Liss, Inc.