Nerve growth factor signaling through p75 induces apoptosis in Schwann cells via a Bcl-2-independent pathway

Soilu-Hanninen, Merja, Ekert, Paul, Bucci, Tamara, Syroid, Daniel, Bartlett, Perry F. and Kilpatrick, Trevor J. (1999) Nerve growth factor signaling through p75 induces apoptosis in Schwann cells via a Bcl-2-independent pathway. Journal of Neuroscience, 19 12: 4828-4838.

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Author Soilu-Hanninen, Merja
Ekert, Paul
Bucci, Tamara
Syroid, Daniel
Bartlett, Perry F.
Kilpatrick, Trevor J.
Title Nerve growth factor signaling through p75 induces apoptosis in Schwann cells via a Bcl-2-independent pathway
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 1999-06-15
Year available 1999
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 19
Issue 12
Start page 4828
End page 4838
Total pages 11
Place of publication Washington, DC, United States
Publisher Society for Neuroscience
Language eng
Formatted abstract
Apoptosis is involved in the regulation of Schwann cell numbers during normal development and after axonal damage, but the molecular regulation of Schwann cell death remains unknown. We have used stably transfected rat Schwann cell lines to study the potential roles of nerve growth factor (NGF), the antiapoptotic protein Bcl-2 and the cytokine response modifier A (CrmA) in modulating Schwann cell death in vitro. Bcl-2 inhibited Schwann cell apoptosis induced by survival factor withdrawal, whereas CrmA did not. In contrast, Bcl-2-transfected Schwann cells were susceptible to apoptosis in response to exogenous NGF, whereas CrmA-expressing cell lines were resistant. Demonstration of high levels of the low-affinity neurotrophin receptor p75 but not the high-affinity TrkA receptor on the Bcl-2-transfected cell lines suggested that the NGF-induced killing was mediated by p75. This was confirmed by resistance of Schwann cells isolated from p75 knockout mice to the NGF-induced cell death. Nerve growth factor also promoted the death of wild-type mouse and rat Schwann cells in the absence of survival factor withdrawal. Endogenous Bcl-2 mRNA was expressed by wild-type Schwann cells in all conditions that promoted survival but was downregulated to undetectable levels after survival factor withdrawal. In conclusion, our results demonstrate the existence of two separate pathways that expedite apoptosis in Schwann cells: a Bcl-2-blockable pathway initiated on loss of trophic support, and a Bcl-2-independent, CrmA-blockable pathway mediated via the p75 receptor.
Keyword Apoptosis
Schwann cells
Nerve growth factor
Low-affinity neurotrophin receptor
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 108 times in Thomson Reuters Web of Science Article | Citations
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