Oxidative Stress Modulates Tyrosine Kinase Receptor A and p75 Receptor (Low-Affinity Nerve Growth Factor Receptor) Expression in SHSY5Y Neuroblastoma Cells

G. Olivieri
U. Otten
F. Meier
G. Baysang
B. Dimitriades-Schmutz
F. Müller-Spahn
E. Savaskan

Published: May 2002

The interaction of neurotrophins and their tyrosine kinase receptors (trks) is essential for differentiation and survival of brain cells. In Alzheimer’s disease (AD), the number of neurotrophins and receptors is markedly decreased. The cause of this reduction is unclear, but the role of ß-amyloid (Aß) seems central in understanding the mechanisms controlling neurotrophin and trk expression. In the study reported here, we exposed SHSY 5 Y neuroblastoma cells to A b or hydrogen peroxide (H ₂ O ₂ ) and measured the expression of trk-A and p75 at the protein and molecular levels. Both A b and H ₂ O ₂ induced oxidative stress (measured by a decrease in cellular glutathione), which decreased trk-A levels and increased p75 levels, decreased messenger RNA (mRNA)levels of both receptors, and increased nerve growth factor (NGF) secretion. Pretreatment of cells with the antioxidant melatonin returned levels of protein expression, mRNA, and NGF secretion to normal. These results are signi?cant, as they can help in the planning and implementation of AD treatment strategies involving neurotrophins.

Keywords: tyrosine kinase receptor A (trk-A), p 75 , ß-amyloid (Aß), melatonin, Alzheimer’s disease (AD), oxidative stress, SHSY5Y neuroblastoma cells