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Nerve growth factor (NGF) and pro-NGF increase low-density lipoprotein (LDL) receptors in neuronal cells partly by different mechanisms : role of LDL in neurite outgrowth
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- Do, Hai Thi (author)
- Department of Biochemistry and Developmental Biology, Medical Faculty, Medicum, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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- Bruelle, Celine (author)
- Department of Biochemistry and Developmental Biology, Medical Faculty, Medicum, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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- Pham, Dan Duc (author)
- Department of Biochemistry and Developmental Biology, Medical Faculty, Medicum, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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- (creator_code:org_t)
- 2015-11-19
- 2016
- English.
- In: Journal of Neurochemistry. - : WILEY. - 0022-3042 .- 1471-4159. ; 136:2, s. 306-315
- Journal article (peer-reviewed)
Abstract
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- Low-density lipoprotein receptors (LDLRs) mediate the uptake of lipoprotein particles into cells, as studied mainly in peripheral tissues. Here, we show that nerve growth factor (NGF) increases LDLR levels in PC6.3 cells and in cultured septal neurons from embryonic rat brain. Study of the mechanisms showed that NGF enhanced transcription of the LDLR gene, acting mainly via Tropomyosin receptor kinase A receptors. Simvastatin, a cholesterol-lowering drug, also increased the LDLR expression in PC6.3 cells. In addition, pro-NGF and pro-brain-derived neurotrophic factor, acting via the p75 neurotrophin receptor (p75NTR) also increased LDLRs. We further observed that Myosin Regulatory Light Chain-Interacting Protein/Inducible Degrader of the LDLR (Mylip/Idol) was down-regulated by pro-NGF, whereas the other LDLR regulator, proprotein convertase subtilisin kexin 9 (PCSK9) was not significantly changed. On the functional side, NGF and pro-NGF increased lipoprotein uptake by neuronal cells as shown using diacetyl-labeled LDL. The addition of serum-derived lipoprotein particles in conjunction with NGF or simvastatin enhanced neurite outgrowth. Collectively, these results show that NGF and simvastatin are able to stimulate lipoprotein uptake by neurons with a positive effect on neurite outgrowth. Increases in LDLRs and lipoprotein particles in neurons could play a functional role during brain development, in neuroregeneration and after brain injuries.
Keyword
- LDLR
- Mylip
- Idol
- NGF
- PCSK9
- pro-BDNF
- pro-NGF
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- ref (subject category)
- art (subject category)
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