Suppression of p140trkA does not abolish nerve growth factor-mediated rescue of serum-free PC12 cells

Giulio Taglialatela, Chris J. Hibbert, Leslie A. Hutton, Karin Werrbach-Perez, J. Regino Perez-Polo

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)1826-1835
Number of pages10
JournalJournal of Neurochemistry
Volume66
Issue number5
StatePublished - May 1996

Fingerprint

PC12 Cells
Nerve Growth Factors
Nerve Growth Factor
Apoptosis
Brain-Derived Neurotrophic Factor
Receptor Protein-Tyrosine Kinases
Serum
Phosphorylation
Protein-Tyrosine Kinases
Bearings (structural)
trkB Receptor
Neurotrophin 3
Nerve Growth Factor Receptors
Antisense Oligonucleotides
Pathology
Cell death
Neurons
Cell Death

Keywords

  • Aging
  • Antisense oligonucleotide
  • Apoptosis
  • Neurotrophin
  • p75-
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Taglialatela, G., Hibbert, C. J., Hutton, L. A., Werrbach-Perez, K., & Perez-Polo, J. R. (1996). Suppression of p140trkA does not abolish nerve growth factor-mediated rescue of serum-free PC12 cells. Journal of Neurochemistry, 66(5), 1826-1835.

Suppression of p140trkA does not abolish nerve growth factor-mediated rescue of serum-free PC12 cells. / Taglialatela, Giulio; Hibbert, Chris J.; Hutton, Leslie A.; Werrbach-Perez, Karin; Perez-Polo, J. Regino.

In: Journal of Neurochemistry, Vol. 66, No. 5, 05.1996, p. 1826-1835.

Research output: Contribution to journalArticle

Taglialatela, G, Hibbert, CJ, Hutton, LA, Werrbach-Perez, K & Perez-Polo, JR 1996, 'Suppression of p140trkA does not abolish nerve growth factor-mediated rescue of serum-free PC12 cells', Journal of Neurochemistry, vol. 66, no. 5, pp. 1826-1835.
Taglialatela, Giulio ; Hibbert, Chris J. ; Hutton, Leslie A. ; Werrbach-Perez, Karin ; Perez-Polo, J. Regino. / Suppression of p140trkA does not abolish nerve growth factor-mediated rescue of serum-free PC12 cells. In: Journal of Neurochemistry. 1996 ; Vol. 66, No. 5. pp. 1826-1835.
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