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Suppression of p140 trkA Does Not Abolish Nerve Growth Factor‐Mediated Rescue of Serum‐Free PC12 Cells
Author(s) -
Taglialatela Giulio,
Hibbert Chris J.,
Hutton Leslie A.,
WerrbachPerez Karin,
PerezPolo J. Regino
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66051826.x
Subject(s) - trk receptor , tropomyosin receptor kinase a , tropomyosin receptor kinase b , nerve growth factor , neurotrophin , low affinity nerve growth factor receptor , neurotrophic factors , brain derived neurotrophic factor , apoptosis , receptor , biology , programmed cell death , neurodegeneration , tropomyosin receptor kinase c , microbiology and biotechnology , medicine , endocrinology , growth factor , platelet derived growth factor receptor , biochemistry , disease
Programmed 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 p75 NGFR , 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 p75 NGFR ‐bearing cells blocks apoptosis but also suggest that if Trk receptors are expressed, prohibiting Trk phosphorylation also blocks NT‐mediated rescue from apoptosis.