Suppression of p140trkA Does Not Abolish Nerve Growth Factor-Mediated Rescue of Serum-Free PC12 Cells

Authors

  • Giulio Taglialatela,

    Corresponding author
    1. Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch at Galveston, Galveston, Texas, U.S.A.
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  • Chris J. Hibbert,

    1. Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch at Galveston, Galveston, Texas, U.S.A.
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    • The present address of Dr. C. J. Hibbert is School of Biology and Biochemistry, University of Bath, Bath, U.K.

  • Leslie A. Hutton,

    1. Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch at Galveston, Galveston, Texas, U.S.A.
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  • Karin Werrbach-Perez,

    1. Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch at Galveston, Galveston, Texas, U.S.A.
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  • J. Regino Perez-Polo

    1. Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch at Galveston, Galveston, Texas, U.S.A.
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Address correspondence and reprint requests to Dr. G. Taglialatela at Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch at Galveston, Galveston, TX 77555-0652, U.S.A.

Abstract

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.

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