• G Taglialatela, C J Hibbert, L A Hutton, K Werrbach-Perez, and J R Perez-Polo.
• Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch at Galveston 77555-0652, USA.
• J. Neurochem. 1996 May 1; 66 (5): 1826-35.

AbstractProgrammed cell death, the intrinsic form of apoptosis, plays an integral role in those neurodegenerative events associated with age-related neuropathology. Neurotrophins (NTs), such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3, are required for survival of certain neurons, and thus their clinical use to counteract age- and pathology-associated neurodegeneration has been suggested, although mechanistic descriptions for NT cell rescue from apoptosis are not definitive. Here we attempted to isolate the individual actions of high-affinity tyrosine kinase (Trk) receptors and p75NGFR, the common low-affinity NT receptor, in NT rescue of apoptotic PC12 cells. Our results showed that whereas inhibiting Trk receptor phosphorylation abolishes NGF rescue of serum-deprived PC12 cells from apoptosis, TrkA suppression with antisense oligonucleotides did not. Also, although BDNF did not rescue naive serumless PC12 cells, which lack the BDNF-specific TrkB receptor, it significantly increased survival of TrkA-suppressed serum-starved PC12 cells. These data confirm the hypothesis that binding of any NT to Trk-free p75NGFR-bearing cells blocks apoptosis but also suggest that if Trk receptors are expressed, prohibiting Trk phosphorylation also blocks NT-mediated rescue from apoptosis.

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