Pigment epithelium‐derived factor (PEDF) differentially protects immature but not mature cerebellar granule cells against apoptotic cell death

Pigment epithelium‐derived factor (PEDF) differentially protects immature but not mature... We have shown previously that pigment epithelium‐derived factor (PEDF) acts as a survival factor for cerebellar granule cell neurons in culture, as well as protecting them against glutamate toxicity. In this study we have examined effects of PEDF on apoptotic cell death. We find that the granule cells die of apoptosis throughout the culture period, what we have termed “natural” apoptosis. PEDF prevents this natural apoptosis if added to immature cells, within the first 2 days in vitro (DIV), and the effect is maintained for up to DIV12. However, PEDF has no effect if added to mature cells at DIV5. Similar results are obtained when apoptosis is induced by shifting the cells from a serum‐ and 25 mM KCl‐containing medium to serum‐free medium with 5 mM KCl. PEDF most effectively blocks induced apoptosis in immature cells (DIV2) when added 24 hr prior to the change of medium, but still provides some protection when added simultaneously. However, 24 hr pretreatment with PEDF has a minimal effect when apoptosis is induced in mature DIV6 cells; addition at the same time is completely ineffective. Two polypeptide fragments of PEDF, only one of which contains the serine‐protease inhibitory site, are equally active, supporting previous results which suggest that the neurotrophic effects of PEDF are not mediated by protease inhibition. We conclude that PEDF protects immature but not mature granule cells against both natural and induced apoptosis. J. Neurosci. Res. 53:7–15, 1998. Published 1998 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neuroscience Research Wiley

Pigment epithelium‐derived factor (PEDF) differentially protects immature but not mature cerebellar granule cells against apoptotic cell death

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Publisher
Wiley
Copyright
Published 1998 Wiley‐Liss, Inc.
ISSN
0360-4012
eISSN
1097-4547
DOI
10.1002/(SICI)1097-4547(19980701)53:1<7::AID-JNR2>3.0.CO;2-F
Publisher site
See Article on Publisher Site

Abstract

We have shown previously that pigment epithelium‐derived factor (PEDF) acts as a survival factor for cerebellar granule cell neurons in culture, as well as protecting them against glutamate toxicity. In this study we have examined effects of PEDF on apoptotic cell death. We find that the granule cells die of apoptosis throughout the culture period, what we have termed “natural” apoptosis. PEDF prevents this natural apoptosis if added to immature cells, within the first 2 days in vitro (DIV), and the effect is maintained for up to DIV12. However, PEDF has no effect if added to mature cells at DIV5. Similar results are obtained when apoptosis is induced by shifting the cells from a serum‐ and 25 mM KCl‐containing medium to serum‐free medium with 5 mM KCl. PEDF most effectively blocks induced apoptosis in immature cells (DIV2) when added 24 hr prior to the change of medium, but still provides some protection when added simultaneously. However, 24 hr pretreatment with PEDF has a minimal effect when apoptosis is induced in mature DIV6 cells; addition at the same time is completely ineffective. Two polypeptide fragments of PEDF, only one of which contains the serine‐protease inhibitory site, are equally active, supporting previous results which suggest that the neurotrophic effects of PEDF are not mediated by protease inhibition. We conclude that PEDF protects immature but not mature granule cells against both natural and induced apoptosis. J. Neurosci. Res. 53:7–15, 1998. Published 1998 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.

Journal

Journal of Neuroscience ResearchWiley

Published: Jul 1, 1998

References

  • Removal of serum from primary cultures of cerebellar granule neurons induces oxidative stress and DNA fragmentation: Protection with antioxidants and glutamate receptor antagonists
    Atabay, Atabay; Cagnoli, Cagnoli; Kharlamov, Kharlamov; Ikonomovic, Ikonomovic; Manev, Manev
  • Neuronal apoptosis
    Bredesen, Bredesen
  • Brain‐derived neurotrophic factor is a survival factor for cultured rat cerebellar granule neurons and protects them against glutamate‐induced neurotoxicity
    Lindholm, Lindholm; Dechant, Dechant; Heisenberg, Heisenberg; Thoenen, Thoenen
  • Cell death: The significance of apoptosis
    Wyllie, Wyllie; Kerr, Kerr; Currie, Currie

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