Nicergoline stimulates protein kinase C mediated α-secretase processing of the amyloid precursor protein in cultured human neuroblastoma SH-SY5Y cells

Cedazo-Minguez, Ángel; Bonecchi, Loredana; Winblad, Bengt; Post, Claes; Wong, Eric H. F.; Cowburn, Richard F.; Benatti, Luca

doi:10.1016/s0197-0186(99)00074-1

Cited by 23 publications

(14 citation statements)

References 33 publications

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“…Although much work on amyloid metabolism has been carried out using the human neuroblastoma SH-SY5Y cell line (originally sub-cloned from a neuroblastic (N)-type human neuroepithelioma cell line, SK-N-SH) which expresses APP and is a convenient and commonly used model for analysing APP processing by secretases under various experimental conditions by Youdim and colleagues [19,20] and others [8,21], the present study revealed that levels of the amyloid-degrading enzyme NEP protein expression in these cells are negligible. Further analysis of various human neuroblastoma cell lines demonstrated that NB7 cells derived from neuroblastic (Ntype) SJ-N-CG cell line possessed a significantly high level of endogenous NEP and other amyloid-degrading enzymes e.g.…”

Section: Discussionmentioning

confidence: 99%

Effects of Hypoxia and Oxidative Stress on Expression of Neprilysin in Human Neuroblastoma Cells and Rat Cortical Neurones and Astrocytes

et al. 2007

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Pathogenesis of Alzheimer's disease (AD), which is characterised by accumulation of extracellular deposits of beta-amyloid peptide (Abeta) in the brain, has recently been linked to vascular disorders such as ischemia and stroke. Abeta is constantly produced in the brain from amyloid precursor protein (APP) through its cleavage by beta- and gamma-secretases and certain Abeta species are toxic for neurones. The brain has an endogenous mechanism of Abeta removal via proteolytic degradation and the zinc metalloproteinase neprilysin (NEP) is a critical regulator of Abeta concentration. Down-regulation of NEP could predispose to AD. By comparing the effects of hypoxia and oxidative stress on expression and activity of the Abeta-degrading enzyme NEP in human neuroblastoma NB7 cells and rat primary cortical neurones we have demonstrated that hypoxia reduced NEP expression at the protein and mRNA levels as well as its activity. On contrary in astrocytes hypoxia increased NEP mRNA expression.

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Section: Discussionmentioning

confidence: 99%

Effects of Hypoxia and Oxidative Stress on Expression of Neprilysin in Human Neuroblastoma Cells and Rat Cortical Neurones and Astrocytes

et al. 2007

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“…Recently, JollyTornetta and Wolf (34) reported loss of PMA-regulated APPs secretion after PMA-induced down-regulation of PKC␣ in Ntera 2 neurons and down-regulation of PKC␣ and PKC⑀ in CHO cells expressing APP 695 . Also, Cedazo-Minquez et al, (46) recently reported that phorbol ester stimulated secretion of APPs in SH-SY5Y neuroblastoma cells is reduced by Gö 6976, which inhibits PKC␣, PKC␤I, PKC␤II, PKC␥ (41), and PKC, (42). However, in neither of these studies did the investigators selectively manipulate individual PKC isozymes or examine A␤ levels.…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase C ϵ Suppresses Aβ Production and Promotes Activation of α-Secretase

Zhu

Wang

Lin

et al. 2001

Biochemical and Biophysical Research Communications

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“…Detection of α-secretase processed APP (α-APP) was performed as previously described. 56 75 µl medium of each sample was loaded to the gels. Immunoblotting was performed as described elsewhere 57 using primary antibodies at 1:1000 dilution: anti-Aβ 1-17 (6E10, Signet Laboratories, SIG-39320), anti-lysosomal associated membrane protein-2 (CD107b/ LAMP-2, Southern Biotechnology, 9840-01), anti-autophagy related protein LC3B (LC3, Novus Biologicals, NB600-1384B), anti-p70 S6 Kinase (Cell Signaling, 9202S), anti-Phospho-p70 S6 Kinase (Cell signaling, 9206S), or anti-actin (Sigma-Aldrich, A 2668).…”

Section: Methodsmentioning

confidence: 99%

Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells

et al. 2011

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) Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidantinduced apoptosis of cultured neuroblastoma cells, Autophagy, 7:12, 1528-1545 To link to this article: https://doi.org/10.4161/auto.7.12.18051 Do not distribute.Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells Keywords: Alzheimer disease, amyloid β-protein, amyloid precursor protein, apoptosis, autophagy, lysosomes, oxidative stressAbbreviations: 3MA, 3-methyladenine; AD, Alzheimer disease; ATG5, autophagy-related protein 5; Aβ, amyloid β-protein; APP, amyloid precursor protein; NH4Cl, ammonium chloride; APPwt, wild-type APP695; APPswe, Swedish KM670/671NL double mutation; α-APP, α-secretase processed APP; DAPT, LY-374973, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester; DCF, carboxy-H 2 DCFDA; DAPI, 4' 6-diamidino-2-phenylindole; E64d, (2S,3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester, EST; HEK, human embryonic kidney; LAMP-2, lysosomal associated membrane protein-2; LC3, microtubule-associated protein 1 light chain 3; NFT, neurofibrillary tangles; RA, retinoic acid; ROS, reactive oxygen speciesIncreasing evidence suggests the toxicity of intracellular amyloid β-protein (Aβ) to neurons, as well as the involvement of oxidative stress in Alzheimer disease (AD). Here we show that normobaric hyperoxia (exposure of cells to 40% oxygen for five days, and consequent activation of macroautophagy and accumulation of Aβ within lysosomes, induced apoptosis in differentiated SH-SY5Y neuroblastoma cells. Cells under hyperoxia showed: (1) increased numbers of autophagic vacuoles that contained amyloid precursor protein (APP) as well as Aβ monomers and oligomers, (2) increased reactive oxygen species production, and (3) enhanced apoptosis. Oxidant-induced apoptosis positively correlated with cellular Aβ production, being the highest in cells that were stably transfected with APP Swedish KM670/671NL double mutation. Inhibition of γ-secretase, prior and/or in parallel to hyperoxia, suggested that the increase of lysosomal Aβ resulted mainly from its autophagic uptake, but also from APP processing within autophagic vacuoles. The oxidative stress-mediated effects were prevented by macroautophagy inhibition using 3-methyladenine or ATG5 downregulation. Our results suggest that upregulation of macroautophagy and resulting lysosomal Aβ accumulation are essential for oxidant-induced apoptosis in cultured neuroblastoma cells and provide additional support for the interactive role of oxidative stress and the lysosomal system in AD-related neurodegeneration.

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Nicergoline stimulates protein kinase C mediated α-secretase processing of the amyloid precursor protein in cultured human neuroblastoma SH-SY5Y cells

Cited by 23 publications

References 33 publications

Effects of Hypoxia and Oxidative Stress on Expression of Neprilysin in Human Neuroblastoma Cells and Rat Cortical Neurones and Astrocytes

Effects of Hypoxia and Oxidative Stress on Expression of Neprilysin in Human Neuroblastoma Cells and Rat Cortical Neurones and Astrocytes

Protein Kinase C ϵ Suppresses Aβ Production and Promotes Activation of α-Secretase

Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells

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