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Multiple Distinct Signal Pathways, Including an Autocrine Neurotrophic Mechanism, Contribute to the Survival-Promoting Effect of Depolarization on Spiral Ganglion Neurons In Vitro
DC Field | Value | Language |
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dc.contributor.author | 복진웅 | - |
dc.date.accessioned | 2016-02-19T11:27:30Z | - |
dc.date.available | 2016-02-19T11:27:30Z | - |
dc.date.issued | 2001 | - |
dc.identifier.issn | 0270-6474 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/143187 | - |
dc.description.abstract | We have shown previously that BDNF, neurotrophin-3 (NT-3), chlorphenylthio-cAMP (cpt-cAMP) (a permeant cAMP analog), and membrane depolarization promote spiral ganglion neuron (SGN) survival in vitro in an additive manner, depolarization having the greatest efficacy. Expression of both BDNF and of NT-3 is detectable in cultured SGNs after plating in either depolarizing or nondepolarizing medium. These neurotrophins promote survival by an autocrine mechanism; TrkB-IgG or TrkC-IgG, which block neurotrophin binding to, respectively, TrkB and TrkC, partially inhibit the trophic effect of depolarization. The mitogen-activated protein kinase kinase inhibitor PD98059 and the phosphatidylinositol-3-OH kinase inhibitor LY294002 both abolish trophic support by neurotrophins but only partially inhibit support by depolarization. Inhibition by these compounds is not additive with inhibition by Trk-IgGs. The cAMP antagonist Rp-adenosine-3′,5′-cyclic-phosphorothioate (Rp-cAMPS) abolishes survival attributable to cpt-cAMP but has no effect on that attributable to neurotrophins, nor do inhibitors of neurotrophin-dependent survival affect survival attributable to cpt-cAMP. However, Rp-cAMPS does partially inhibit depolarization-dependent survival, an inhibition that is additive with that by Trk-IgGs, PD98059, or LY294002. Moreover, Rp-cAMPS prevents depolarization-dependent survival of PC12 cells maintained in subthreshold levels of NGF. Inhibition of Ca2+/calmodulin-dependent protein kinases (CaMKs) with KN-62 reduces SGN survival independently of Rp-cAMPS, Trk-IgGs, and LY294002 and additively with them. Combined inhibition of Trk, cAMP, and CaMK signaling prevents depolarization-dependent survival. Thus, survival of SGNs under depolarizing conditions involves additivity among a depolarization-independent autocrine pathway, a cAMP-dependent pathway, and a CaMK-dependent pathway. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 2256~2267 | - |
dc.relation.isPartOf | JOURNAL OF NEUROSCIENCE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Autocrine Communication/physiology* | - |
dc.subject.MESH | Cell Survival/physiology | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Cyclic AMP/physiology | - |
dc.subject.MESH | Membrane Potentials/physiology* | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Signal Transduction/physiology* | - |
dc.subject.MESH | Spiral Ganglion/physiology* | - |
dc.title | Multiple Distinct Signal Pathways, Including an Autocrine Neurotrophic Mechanism, Contribute to the Survival-Promoting Effect of Depolarization on Spiral Ganglion Neurons In Vitro | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Anatomy (해부학) | - |
dc.contributor.googleauthor | Marlan R. Hansen | - |
dc.contributor.googleauthor | Xiang-Ming Zha | - |
dc.contributor.googleauthor | Jinwoong Bok | - |
dc.contributor.googleauthor | Steven H. Green | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01865 | - |
dc.relation.journalcode | J01633 | - |
dc.identifier.eissn | 1529-2401 | - |
dc.identifier.pmid | 11264301 | - |
dc.contributor.alternativeName | Bok, Jin Woong | - |
dc.contributor.affiliatedAuthor | Bok, Jin Woong | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 21 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 2256 | - |
dc.citation.endPage | 2267 | - |
dc.identifier.bibliographicCitation | JOURNAL OF NEUROSCIENCE, Vol.21(7) : 2256-2267, 2001 | - |
dc.identifier.rimsid | 39122 | - |
dc.type.rims | ART | - |
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