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

• Published in: Journal of neuroscience research Vol. 72; no. 1; pp. 89 - 97
• Main Authors: Dennis, Jameel, Bennett Jr, James P.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.04.2003
• Subjects: Apoptosis - drug effects; Apoptosis - physiology; Bcl-2 proteins; bcl-2-Associated X Protein; Humans; mitochondria; MPP; Neuroblastoma - metabolism; Neurons - drug effects; Neurons - metabolism; nitric oxide; Nitric Oxide - metabolism; Nitric Oxide - pharmacology; Parkinson's disease; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - metabolism; Pyridinium Compounds - pharmacology; SY5Y cells; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - metabolism
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.10540

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‐XL proteins. Like MPP+, DETA‐NO caused an early decrease in Bcl‐2 mRNA, did not increase Bax protein in ρ0 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‐XL 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.