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Article: Neuroprotective signaling mechanisms of telomerase are regulated by brain-derived neurotrophic factor in rat spinal cord motor neurons

TitleNeuroprotective signaling mechanisms of telomerase are regulated by brain-derived neurotrophic factor in rat spinal cord motor neurons
Authors
KeywordsApoptosis
Brain-derived neurotrophic factor
Neuronal survival
Spinal cord motor neuron
Telomerase
Issue Date2011
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.jneuropath.com
Citation
Journal Of Neuropathology And Experimental Neurology, 2011, v. 70 n. 7, p. 634-652 How to Cite?
AbstractTelomerase can promote neuron survival and can be regulated by growth factors such as brain-derived neurotrophic factor (BDNF). Increases of BDNF expression and telomerase activity after brain injury suggest that telomerase may be involved in BDNF-mediated neuroprotection. We investigated BDNF regulation of telomerase in rat spinal cord motor neurons (SMNs). Our results indicate that BDNF increases telomerase expression and activity levels in SMNs and activates mitogen-activated protein kinase/extracellular signal-regulated kinases 1 and 2 and phosphatidylinositol-3-OH kinase/protein kinase B signals, and their downstream transcription factors nuclear factor-κB, c-Myc, and Sp1. Administration of the tyrosine kinase receptor B inhibitor K-252a, the mitogen-activated protein kinase 1 inhibitor PD98059, and the phosphatidylinositol-3-OH kinase inhibitor LY294002 abolished BDNF-induced upregulation of these transcription factors and telomerase expression. The nuclear factor-κB inhibitor Bay11-7082 also attenuated c-Myc and Sp1 expression and increased telomerase promoter activity. Spinal cord motor neurons with higher telomerase levels induced by BDNF became more resistant to apoptosis; survival of SMNs that overexpressed the catalytic protein component of telomerase with reverse transcriptase activity was also enhanced against apoptosis. The neuronal survival-promoting effect of telomerase was mediated through the regulation of Bcl-2, Bax, p53, and maintenance of mitochondrial membrane potential. Taken together, these data suggest that the neuroprotective effect of BDNF via telomerase is mediated by inhibition of apoptotic pathways. Copyright © 2011 by the American Association of Neuropathologists, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/137207
ISSN
2015 Impact Factor: 3.432
2015 SCImago Journal Rankings: 2.136
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorNiu, Cen_HK
dc.contributor.authorYip, HKen_HK
dc.date.accessioned2011-08-26T14:18:48Z-
dc.date.available2011-08-26T14:18:48Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Neuropathology And Experimental Neurology, 2011, v. 70 n. 7, p. 634-652en_HK
dc.identifier.issn0022-3069en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137207-
dc.description.abstractTelomerase can promote neuron survival and can be regulated by growth factors such as brain-derived neurotrophic factor (BDNF). Increases of BDNF expression and telomerase activity after brain injury suggest that telomerase may be involved in BDNF-mediated neuroprotection. We investigated BDNF regulation of telomerase in rat spinal cord motor neurons (SMNs). Our results indicate that BDNF increases telomerase expression and activity levels in SMNs and activates mitogen-activated protein kinase/extracellular signal-regulated kinases 1 and 2 and phosphatidylinositol-3-OH kinase/protein kinase B signals, and their downstream transcription factors nuclear factor-κB, c-Myc, and Sp1. Administration of the tyrosine kinase receptor B inhibitor K-252a, the mitogen-activated protein kinase 1 inhibitor PD98059, and the phosphatidylinositol-3-OH kinase inhibitor LY294002 abolished BDNF-induced upregulation of these transcription factors and telomerase expression. The nuclear factor-κB inhibitor Bay11-7082 also attenuated c-Myc and Sp1 expression and increased telomerase promoter activity. Spinal cord motor neurons with higher telomerase levels induced by BDNF became more resistant to apoptosis; survival of SMNs that overexpressed the catalytic protein component of telomerase with reverse transcriptase activity was also enhanced against apoptosis. The neuronal survival-promoting effect of telomerase was mediated through the regulation of Bcl-2, Bax, p53, and maintenance of mitochondrial membrane potential. Taken together, these data suggest that the neuroprotective effect of BDNF via telomerase is mediated by inhibition of apoptotic pathways. Copyright © 2011 by the American Association of Neuropathologists, Inc.en_HK
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.jneuropath.comen_HK
dc.relation.ispartofJournal of Neuropathology and Experimental Neurologyen_HK
dc.subjectApoptosisen_HK
dc.subjectBrain-derived neurotrophic factoren_HK
dc.subjectNeuronal survivalen_HK
dc.subjectSpinal cord motor neuronen_HK
dc.subjectTelomeraseen_HK
dc.subject.meshApoptosis - drug effects - physiology-
dc.subject.meshBrain-Derived Neurotrophic Factor - pharmacology-
dc.subject.meshMotor Neurons - drug effects-
dc.subject.meshSpinal Cord - cytology-
dc.subject.meshTelomerase - metabolism-
dc.titleNeuroprotective signaling mechanisms of telomerase are regulated by brain-derived neurotrophic factor in rat spinal cord motor neuronsen_HK
dc.typeArticleen_HK
dc.identifier.emailYip, HK:hkfyip@hku.hken_HK
dc.identifier.authorityYip, HK=rp00285en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/NEN.0b013e318222b97ben_HK
dc.identifier.pmid21666495-
dc.identifier.scopuseid_2-s2.0-79959509244en_HK
dc.identifier.hkuros191959en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79959509244&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume70en_HK
dc.identifier.issue7en_HK
dc.identifier.spage634en_HK
dc.identifier.epage652en_HK
dc.identifier.eissn1554-6578-
dc.identifier.isiWOS:000291785100008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridNiu, C=49661939900en_HK
dc.identifier.scopusauthoridYip, HK=7101980864en_HK

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