|Nerve growth factor signaling through p75 induces apoptosis in Schwann cells via a Bcl-2-independent pathway.|
|PMID: 10366617 Owner: NLM Status: MEDLINE|
|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.|
|M Soilu-Hänninen; P Ekert; T Bucci; D Syroid; P F Bartlett; T J Kilpatrick|
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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 19 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 1999 Jun|
|Created Date: 1999-06-28 Completed Date: 1999-06-28 Revised Date: 2009-11-19|
Medline Journal Info:
|Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: UNITED STATES|
|Languages: eng Pagination: 4828-38 Citation Subset: IM|
|The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Parkville Victoria 3050, Australia.|
|APA/MLA Format Download EndNote Download BibTex|
Antineoplastic Agents / pharmacology
Apoptosis / drug effects*, genetics
Blood Proteins / pharmacology
Cell Survival / physiology
Forskolin / pharmacology
Gene Expression / physiology
Glycoproteins / pharmacology
Mice, Inbred BALB C
Nerve Growth Factors / pharmacology*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-bcl-2 / genetics, metabolism*
RNA, Messenger / analysis
Receptor Protein-Tyrosine Kinases / genetics
Receptor, Nerve Growth Factor
Receptors, Nerve Growth Factor / genetics, physiology*
Schwann Cells / chemistry, cytology*, physiology
Serpins / genetics
Signal Transduction / physiology
|0/Antineoplastic Agents; 0/Blood Proteins; 0/DNA Primers; 0/Glycoproteins; 0/Nerve Growth Factors; 0/Neuregulins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 0/Receptor, Nerve Growth Factor; 0/Receptors, Nerve Growth Factor; 0/Serpins; 0/Viral Proteins; 66428-89-5/Forskolin; 96282-35-8/interleukin-1beta-converting enzyme inhibitor; EC 220.127.116.11/Receptor Protein-Tyrosine Kinases; EC 18.104.22.168/Receptor, trkA|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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