Distinct signaling pathways of precursor BDNF and mature BDNF in cultured cerebellar granule neurons

Hisatsugu Koshimizu, Shunsuke Hazama, Tomoko Hara, Akihiko Ogura, Masami Kojima

Research output: Contribution to journalArticle

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Abstract

Recent studies have focused on a distinctive contrast between bioactivities of precursor brain-derived neurotrophic factor (proBDNF) and mature BDNF (matBDNF). In this study, using a proteolytic cleavage-resistant proBDNF mutant (CR-proBDNF), signaling mechanisms underlying the proapoptotic effect of proBDNF and antiapoptotic effect of matBDNF on the low potassium (LK)-inducing cell death of cultured cerebellar granule neurons (CGNs) were analyzed. A time course study demonstrated that unlike matBDNF, CR-proBDNF failed to induce TrkB phosphorylation for up to 360min. CR-proBDNF did not activate ERK-1, ERK-2 and Akt, which are involved in TrkB-induced cell survival signaling, while matBDNF activated these kinases. On the other hand treatment of CGNs with CR-proBDNF led to a rapid activation of Rac-GTPase and phosphorylation of JNK which are involved in p75NTR-induced apoptosis. In addition, a JNK-specific inhibitor, SP600125, inhibited the CR-proBDNF-induced apoptosis but did not affect the antiapoptotic effect of matBDNF. CR-proBDNF treatment led to an earlier appearance of active caspase-3. In contrast, matBDNF dramatically postponed the appearance of active caspase-3. Not like other signaling molecules, activation of caspase-3 was conversely regulated by both CR-proBDNF and matBDNF. These results thus suggest that in CGNs proBDNF elicits apoptosis via activation of p75NTR, Rac-GTPase, JNK, and caspase-3, while matBDNF signals cell survival via activation of TrkB, ERKs and Akt, and deactivation of caspase-3.

Original languageEnglish
Pages (from-to)229-232
Number of pages4
JournalNeuroscience Letters
Volume473
Issue number3
DOIs
Publication statusPublished - 01-04-2010

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Brain-Derived Neurotrophic Factor
Neurons
Caspase 3
GTP Phosphohydrolases
Apoptosis
Cell Survival
Phosphorylation
Potassium
Cell Death
Phosphotransferases
brain-derived neurotrophic factor precursor

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Koshimizu, Hisatsugu ; Hazama, Shunsuke ; Hara, Tomoko ; Ogura, Akihiko ; Kojima, Masami. / Distinct signaling pathways of precursor BDNF and mature BDNF in cultured cerebellar granule neurons. In: Neuroscience Letters. 2010 ; Vol. 473, No. 3. pp. 229-232.
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Distinct signaling pathways of precursor BDNF and mature BDNF in cultured cerebellar granule neurons. / Koshimizu, Hisatsugu; Hazama, Shunsuke; Hara, Tomoko; Ogura, Akihiko; Kojima, Masami.

In: Neuroscience Letters, Vol. 473, No. 3, 01.04.2010, p. 229-232.

Research output: Contribution to journalArticle

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AU - Hazama, Shunsuke

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