β-Amyloid-Activated Cell Cycle in SH-SY5Y Neuroblastoma Cells: Correlation with the MAP Kinase Pathway

Frasca, Giampiero; Chiechio, Santina; Vancheri, Carlo; Nicoletti, Ferdinando; Copani, Agata; Sortino, Maria Angela

doi:10.1385/jmn:22:3:231

Cited by 33 publications

(51 citation statements)

References 17 publications

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“…Furthermore, soluble oligomers have been shown to initially stimulate, but later downregulate, ERK in hippocampal slice cultures (Bell et al, 2004), and studies in AD brain and AD mouse models suggest stage-dependent ERK activation followed by loss of active ERK (Dineley et al, 2001;Webster et al, 2006). However, studies investigating the effects of soluble oligomers on either SHSY-5Y neuroblastoma cells (Frasca et al, 2004(Frasca et al, , 2008 or RCNs (Tong et al, 2004; observed the same alterations of the ERK signaling pathway as reported in our work. Importantly, both the sustained activation and downregulation of the ERK survival-promoting pathway are associated with susceptibility to cell death (Dineley et al, 2001;Bell et al, 2004;Chong et al, 2006;Florent et al, 2006;Webster et al, 2006;Ma et al, 2007;Townsend et al, 2007).…”

Section: Discussionsupporting

confidence: 81%

Site-Specific Blockade of RAGE-V_dPrevents Amyloid-β Oligomer Neurotoxicity

et al. 2008

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In the genesis of Alzheimer's disease (AD), converging lines of evidence suggest that amyloid-␤ peptide (A␤) triggers a pathogenic cascade leading to neuronal loss. It was long assumed that A␤ had to be assembled into extracellular amyloid fibrils or aggregates to exert its cytotoxic effects. Over the past decade, characterization of soluble oligomeric A␤ species in the brains of AD patients and in transgenic models has raised the possibility that different conformations of A␤ may contribute to AD pathology via different mechanisms. The receptor for advanced glycation end products (RAGE), a member of the Ig superfamily, is a cellular binding site for A␤. Here, we investigate the role of RAGE in apoptosis induced by distinct well characterized A␤ conformations: A␤ oligomers (A␤Os), A␤ fibrils (A␤Fs), and A␤ aggregates (A␤As). In our in vitro system, treatment with polyclonal anti-RAGE antibodies significantly improves SHSY-5Y cell and neuronal survival exposed to either A␤Os or A␤As but does not affect A␤F toxicity. Interestingly, using site-specific antibodies, we demonstrate that targeting of the V d domain of RAGE attenuates A␤O-induced toxicity in both SHSY-5Y cells and rat cortical neurons, whereas inhibition of A␤A-induced apoptosis requires the neutralization of the C 1d domain of the receptor. Thus, our data indicate that distinct regions of RAGE are involved in A␤-induced cellular and neuronal toxicity with respect to the A␤ aggregation state, and they suggest the blockage of particular sites of the receptor as a potential therapeutic strategy to attenuate neuronal death.

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Section: Discussionsupporting

confidence: 81%

Site-Specific Blockade of RAGE-V_dPrevents Amyloid-β Oligomer Neurotoxicity

et al. 2008

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“…Cytotoxicity and altered cell cycle status have not been reported following exposure to OP esters, but occur with a variety of other compounds in a number of systems used for study of the nervous system, including rat cortical neurons [21], SY5Y neuroblastoma cells [22,23], PC12 cells, sympathetic neurons, and cerebral cortical neurons [24]. Unscheduled activation can also elicit cytotoxic responses in postmitotic neural cells.…”

Section: Introductionmentioning

confidence: 99%

Distribution of SH‐SY5Y human neuroblastoma cells in the cell cycle following exposure to organophosphorus compounds

Carlson

Ehrich

2008

J Biochem & Molecular Tox

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The current study investigated the relationship of the cell cycle phase (as G(0)/G(1), S, and G(2)/M) and cytotoxicity (as sub-G(1) DNA) to determine whether alterations in cell replication were associated with organophosphate (OP) compound induced cytotoxicity. Results demonstrated that, overall, OP compound--induced cell cycle changes were variable and depended on the OP compound, exposure concentration, and temporal relationship to cytotoxicity. Noncytotoxic OP compound treatments substantially decreased the percentage of cells in S phase of the cell cycle when compared to controls. A corresponding increase was seen in the percent of cells in G(0)/G(1) phase of the cell cycle. In the precytotoxic interval of exposure, most cytotoxic OP compound treatments substantially decreased the percentage of cells in G(2)/M phase of the cell cycle. Corresponding increases were seen primarily in G(0)/G(1) phase cells. Effects on cells in S stage of the cell cycle varied with the OP compound. In the during cytotoxic interval of exposure, most cytotoxic OP compound treatments substantially increased the percentage of cells in S phase of the cell cycle. A corresponding decrease in the percent of cells in G(0)/G(1) stage of the cell cycle was observed. Furthermore, treatments either increased or decreased the percentage of cells in G(2)/M phase of the cell cycle when compared to controls, with decreases more likely with the most cytotoxic OP compound exposures. Overall, the in vitro data suggest that exposure to OP compounds can alter the cell cycle status of SH-SY5Y neuroblastoma cells depending on compound, concentration, and interval from initial exposure. Changes in cell cycle, however, did not differentiate between OP compounds that are known for their ability to acutely inhibit acetylcholinesterase versus those inducing type I and type II delayed neurotoxicity.

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“…These effects are known to be regulated by activation of mitogen-activated protein kinase/ extracellular signal-regulated kinase (MAPK/ERK1/2) pathways [99]. β-Amyloid peptide induces oxidative stress that is associated with the membrane, which causes functional impairment of different receptors, transporters, ion channels, transcription factors and downstream kinases [100].…”

Section: Role Of β-Amyloid Protein In Neu-roblastomamentioning

confidence: 99%