Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation.

Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation. Research Abstract Details 

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Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation. Abstract Text:

M Santra,X Shuang Liu,S Santra,J Zhang,R Lan Zhang,Z Gang Zhang,M Chopp,

Doublecortin (DCX) is a microtubule-associated protein expressed in migrating neuroblasts. DCX expression is increased in subventricular zone (SVZ) cells migrating to the boundary of an ischemic lesion after induction of middle cerebral artery occlusion (MCAO) in adult rats and mice. We tested the hypothesis that DCX, in addition to being a marker of migrating neuroblasts, serves to protect neuroblasts from conditions of stress, such as oxygen and glucose deprivation (OGD). Using gene transfer technology, we overexpressed DCX in rat SVZ and U-87 human glioma cells. The cells remained viable against severe OGD, up to 32 h exhibiting 1% apoptosis compared with 100% apoptosis in control. In addition, these genetically modified cells upregulated expression of E-, VE- and N-cadherin, molecules that promote endothelial survival signals via the VE-cadherin/vascular endothelial growth factor receptor-2/phosphoinositide 3-kinase (PI3-K)/AKT/beta-catenin pathway and inactivate the proapoptotic factor Bad. DCX overexpression also significantly increased cell migration in SVZ tissue explants and U-87 cells and significantly upregulated microtubule-associated protein-2 (MAP2) and nestin protein levels in SVZ and U-87 cells compared with wild-type control cells. Knocking down DCX expression in DCX overexpressing SVZ and U-87 cells with DCX small interfering RNA (siRNA), confirmed the specificity of DCX on cell survival against OGD, and the DCX induced upregulation of E-, VE- and N-cadherin, MAP2 and nestin. In NIH3T3 cells, DCX overexpression had no effect on cell survival against OGD, and indicating that the protective effects of DCX was restricted to brain cells e.g. SVZ and U-87 cells. Our data suggest a novel and an important role for DCX as a protective agent for migrating neuroblasts and tumor cells.

Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation. Publishing Authors By Initials

M Santra,XS Liu,S Santra,J Zhang,RL Zhang,ZG Zhang,M Chopp,

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Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Neuroscience

VOLUME: 142

Page Numbers: 739-52

Journal Abbreviation: Neuroscience

ISSN: 0306-4522

DAY: 8

MONTH: 09

YEAR: 2006

Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation. Information

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LANGUAGE: eng

NlmUniqueID: 7605074

Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation. Keywords Mesh Terms:

KEYWORDS: beta-Galactosidase

MESH TERMS: metabolism

Chemical & Substance for Abstract: Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation. Information

Substance Name: beta-Galactosidase

Registry Number: EC 3.2.1.23

Grant and Affiliation Information for Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation.

AFFILIATION: Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS23393

ACRONYM: NS

MEDLINETA: Neuroscience

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