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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2010.1
- 수록면
- 583 - 595 (13page)
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Neurotrophins protect neurons against excitotoxicity;however the signaling mechanisms for this protection remain to be fully elucidated. Here we report that activation of the phosphatidyl inositol 3 kinase (PI3K)/Akt pathway is critical for protection of hippocampal cells from staurosporine (STS) induced apoptosis, characterized by nuclear condensation and activation of the caspase cascade. Both nerve growth factor (NGF) and brain-derived growth factor (BDNF) prevent STS-induced apoptotic morphology and caspase-3 activity by upregulating phosphorylation of the tropomyosin receptor kinase (Trk) receptor. Inhibition of Trk receptor by K252a altered the neuroprotective effect of both NGF and BDNF whereas inhibition of the p75 neurotrophin receptor (p75NTR) had no effect. Impairment of the PI3K/Akt pathway or overexpression of dominant negative (DN)-Akt abolished the protective effect of both neurotrophins, while active Akt prevented cell death. Moreover, knockdown of Akt by si-RNA was able to block the survival effect of both NGF and BDNF.
Thus, the survival action of NGF and BDNF against STS-induced neurotoxicity was mediated by the activation of PI3K/Akt signaling through the Trk receptor.
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등록된 정보가 없습니다.
참고문헌 (24)
참고문헌 신청
Barbacid M / 1995 / Neurotrophic factors and their receptors / Curr Opin Cell Biol 7 : 148 ~ 155
Bates B / 1999 / Neurotrophin-3 is required for proper cerebellar development / Nat Neurosci 2 : 115 ~ 117
Biggs WH, 3rd / 1999 / Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1 / Proc Natl Acad Sci USA : 7421 ~ 742
Bonni A / 1999 / Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms / Science 286 : 1358 ~ 1362
Brunet A / 1999 / Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor / Cell 96 : 857 ~ 868
Bates B / 1999 / Neurotrophin-3 is required for proper cerebellar development / Nat Neurosci 2 : 115 ~ 117
Biggs WH, 3rd / 1999 / Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1 / Proc Natl Acad Sci USA : 7421 ~ 742
Bonni A / 1999 / Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms / Science 286 : 1358 ~ 1362
Brunet A / 1999 / Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor / Cell 96 : 857 ~ 868
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