Sympathetic neurons synthesize and secrete pro-nerve growth factor protein

Wohaib Hasan, Tetyana Pedchenko, Dora Krizsan-Agbas, Laura Baum, Peter G. Smith

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Postmitotic sympathetic neuronal survival is dependent upon nerve growth factor (NGF) provided by peripheral targets, and this dependency serves as a central tenet of the neurotrophic hypothesis. In some other systems, NGF has been shown to play an autocrine role, although the pervasiveness and significance of this phenomenon within the nervous system remain unclear. We show here that rat sympathetic neurons synthesize and secrete NGF. NGF mRNA is expressed in nearly half of superior cervical ganglion sympathetic neurons at embryonic day 17, rising to over 90% in the early postnatal period, and declining in the adult. Neuronal immunoreactivity is reduced when retrograde transport is interrupted by axotomy, but persists in a subpopulation of neurons despite diminished mRNA expression, suggesting that intrinsic protein synthesis occurs. Cultured neonatal neurons express NGF mRNA, which is maintained even when they are undergoing apoptosis. To determine which NGF isoforms are secreted, we performed metabolic labeling and immunoprecipitation of NGF-immunoreactive proteins synthesized by cultured NGF-dependent and -independent neurons. Conditioned medium contained high molecular weight NGF precursor proteins, which varied depending upon the state of NGF dependence. Mature NGF was undetectable by these methods. High molecular weight NGF isoforms were also detected in ganglion homogenates, and persisted at diminished levels following axotomy. We conclude that sympathetic neurons express NGF mRNA, and synthesize and secrete pro-NGF protein. These findings suggest that a potential NGF-sympathetic neuron autocrine loop may exist in this prototypic target-dependent system, but that the secreted forms of this neurotrophin apparently do not support neuronal survival.

Original languageEnglish (US)
Pages (from-to)38-53
Number of pages16
JournalJournal of Neurobiology
Volume57
Issue number1
DOIs
StatePublished - Oct 2003
Externally publishedYes

Fingerprint

Nerve Growth Factor
Neurons
Proteins
Axotomy
Messenger RNA
Protein Isoforms
Molecular Weight
Superior Cervical Ganglion
Protein Precursors
Nerve Growth Factors
Conditioned Culture Medium
Immunoprecipitation
Ganglia
Nervous System

Keywords

  • Autocrine growth factor
  • Development
  • Nerve growth factor
  • Neuronal survival
  • Sympathetic neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hasan, W., Pedchenko, T., Krizsan-Agbas, D., Baum, L., & Smith, P. G. (2003). Sympathetic neurons synthesize and secrete pro-nerve growth factor protein. Journal of Neurobiology, 57(1), 38-53. https://doi.org/10.1002/neu.10250

Sympathetic neurons synthesize and secrete pro-nerve growth factor protein. / Hasan, Wohaib; Pedchenko, Tetyana; Krizsan-Agbas, Dora; Baum, Laura; Smith, Peter G.

In: Journal of Neurobiology, Vol. 57, No. 1, 10.2003, p. 38-53.

Research output: Contribution to journalArticle

Hasan, W, Pedchenko, T, Krizsan-Agbas, D, Baum, L & Smith, PG 2003, 'Sympathetic neurons synthesize and secrete pro-nerve growth factor protein', Journal of Neurobiology, vol. 57, no. 1, pp. 38-53. https://doi.org/10.1002/neu.10250
Hasan, Wohaib ; Pedchenko, Tetyana ; Krizsan-Agbas, Dora ; Baum, Laura ; Smith, Peter G. / Sympathetic neurons synthesize and secrete pro-nerve growth factor protein. In: Journal of Neurobiology. 2003 ; Vol. 57, No. 1. pp. 38-53.
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