Elsevier

Experimental Neurology

Volume 166, Issue 2, December 2000, Pages 415-421
Experimental Neurology

Regular Article
Synthesis and Regulation of Apolipoprotein E during the Differentiation of Human Neuronal Precursor NT2/D1 Cells into Postmitotic Neurons

https://doi.org/10.1006/exnr.2000.7510Get rights and content

Abstract

Recently, we showed expression of apolipoprotein E (apoE) in human neuronal-type cells such as neuroblastoma SK N SH–SY 5Y cells. In this model, a negative effect of neuronal differentiation on apoE synthesis was suspected. To check this hypothesis, we studied the regulation of apoE in human postmitotic neurons. The presence of apoE was investigated in undifferentiated human teratocarcinoma NT2/D1 (NT2) cells and during their differentiation into postmitotic hNT neurons induced by retinoic acid (RA) treatment. Before differentiation, apoE protein and mRNA were detected in NT2 cells by Western blotting and RT-PCR experiments. Immunofluorescence study showed that apoE was present in all cells. For longer times of RA treatment (3 weeks), the apoE labeling became heterogeneous: only some cells were immunopositive and among them were some differentiating cells in which apoE was located in both cellular body and neuritic process. Interestingly, terminally differentiated hNT cells no longer expressed apoE. These results demonstrate that neuronal precursor and differentiating cells were able to synthesize apoE while the fully neuronal differentiation exerted a negative effect on apoE neuronal expression. Our results are compatible with a weak expression of apoE in neurons of adult brains.

References (41)

Cited by (24)

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  • Astroglial regulation of apolipoprotein E expression in neuronal cells: Implications for Alzheimer's disease

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    Although our current study does not directly address the mechanisms by which the astrocyte-derived factor or factors regulate the transcription of APOE, we speculate that the factor or factors may trigger a signal pathway, such as the Erk pathway, that leads to activation of certain tissue-specific cis-acting regulatory elements of APOE that might be modified by APOE promoter polymorphisms. Based on the current and previous studies (32-39, 41-47), we hypothesize that acute injury, such as head trauma, or chronic injury, such as damage related to amyloid β deposition or oxidative stress, of the CNS causes astroglial proliferation and activation (astrocytosis), leading to secretion of a factor or factors that activate the Erk pathway and induce neuronal expression of apoE (Fig. 7). Neuronal expression of apoE in response to brain injury probably promotes neuronal repair and remodeling and protects neurons from injury (42, 132-134).

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