P3-387 Polychlorinated biphenyls alter expression of Parkinson's disease associated proteins in human neuroblastoma cells and in the rat brain

Much evidence suggests that both oxidative stress and apoptosis play a key role in the pathogenesis of Parkinson’s disease (PD). The present study aims to evaluate the protective effect of bergamot juice (BJ) against 6-hydroxydopamine (6-OHDA)- or H2O2-induced cell death. Treatment of differentiated SH-SY5Y human neuroblastoma cells with 6-OHDA or H2O2 resulted in cell death that was significantly reduced by the pre-treatment with BJ. The protective effects of BJ seem to correlate with the reduction of intracellular reactive oxygen species and nitric oxide generation caused by 6-OHDA or H2O2. BJ also attenuated mitochondrial dysfunction, caspase-3 activation, imbalance of pro- and anti-apoptotic proteins, MAPKs activation and reduced NF-ĸB nuclear translocation evoked by neurotoxic agents. Additionally, BJ exhibited excellent antioxidant capability in cell-free assays. Collectively, our results suggest that BJ exerts neuroprotective effect through the interplay with specific cell targets and its antioxidant activity, making it worthy of consideration for the management of neurodegenerative diseases.

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A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1610586114 ◽

2017 ◽

Vol 114 (6) ◽

pp. E1009-E1017 ◽

Cited By ~ 119

Author(s):

Michele Perni ◽

Céline Galvagnion ◽

Alexander Maltsev ◽

Georg Meisl ◽

Martin B. D. Müller ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Natural Product ◽

Self Assembly ◽

Lipid Membranes ◽

Neuroblastoma Cells ◽

Lipid Vesicles ◽

Human Neuroblastoma

The self-assembly of α-synuclein is closely associated with Parkinson’s disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces α-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process. We also show that squalamine almost completely suppresses the toxicity of α-synuclein oligomers in human neuroblastoma cells by inhibiting their interactions with lipid membranes. We further examine the effects of squalamine in a Caenorhabditis elegans strain overexpressing α-synuclein, observing a dramatic reduction of α-synuclein aggregation and an almost complete elimination of muscle paralysis. These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson’s disease and related conditions.

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Neuroinductive properties of mGDNF depend on the producer, E. Coli or human cells

PLoS ONE ◽

10.1371/journal.pone.0258289 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258289

Author(s):

Dzhirgala V. Shamadykova ◽

Dmitry Y. Panteleev ◽

Nadezhda N. Kust ◽

Ekaterina A. Savchenko ◽

Ekaterina Y. Rybalkina ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Ganglion Cells ◽

Neuroblastoma Cells ◽

Human Cells ◽

Hek293 Cells ◽

Human Neuroblastoma ◽

Mammalian Expression

The glial cell line‐derived neurotrophic factor (GDNF) is involved in the survival of dopaminergic neurons. Besides, GDNF can also induce axonal growth and creation of new functional synapses. GDNF potential is promising for translation to treat diseases associated with neuronal death: neurodegenerative disorders, ischemic stroke, and cerebral or spinal cord damages. Unproductive clinical trials of GDNF for Parkinson’s disease treatment have induced to study this failure. A reason could be due to irrelevant producer cells that cannot perform the required post-translational modifications. The biological activity of recombinant mGDNF produced by E. coli have been compared with mGDNF produced by human cells HEK293. mGDNF variants were tested with PC12 cells, rat embryonic spinal ganglion cells, and SH-SY5Y human neuroblastoma cells in vitro as well as with a mouse model of the Parkinson’s disease in vivo. Both in vitro and in vivo the best neuro-inductive ability belongs to mGDNF produced by HEK293 cells. Keywords: GDNF, neural differentiation, bacterial and mammalian expression systems, cell cultures, model of Parkinson’s disease.

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Inositol 1,3,4,5-tetrakisphosphate-induced release of intracellular Ca2+ in SH-SY5Y neuroblastoma cells

Biochemical Journal ◽

10.1042/bj2720519 ◽

1990 ◽

Vol 272 (2) ◽

pp. 519-524 ◽

Cited By ~ 45

Author(s):

D J Gawler ◽

B V Potter ◽

S R Nahorski

Keyword(s):

Low Temperature ◽

Rat Brain ◽

Neuroblastoma Cells ◽

Detection Limits ◽

Maximal Response ◽

Maximal Effect ◽

Additive Effects ◽

Inositol Polyphosphate ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma

Inositol-polyphosphate-induced Ca2+ mobilization was investigated in saponin-permeabilized SH-SY5Y human neuroblastoma cells. Ins(1,4,5)P3 induced a dose-related release from intracellular Ca2+ stores with an EC50 (concn. giving half-maximal effect) of 0.1 microM and a maximal release of 70%. Ins(1,3,4)P3, DL-Ins(1,4,5,6)P4 and Ins(1,3,4,5,6)P5 did not evoke Ca2+ mobilization in these cells when used at concentrations up to 10 microM. However, Ins(1,3,4,5)P4 was found to release Ca2+ in a dose-related manner, but the response was dependent on the source of Ins(1,3,4,5)P4 used. When commercially available D-Ins(1,3,4,5)P4 was used, the EC50 and maximal response values were 1 microM and 50% respectively, compared with values for chemically synthesized DL-Ins(1,3,4,5)P4 of 2 microM and 25%. The enhanced maximal response of commercial D-Ins(1,3,4,5)P4 was decreased by pretreatment with rat brain crude Ins(1,4,5)P3 3-kinase and was therefore concluded to be indicative of initial Ins(1,4,5)P3 contamination of the Ins(1,3,4,5)P4 preparation. When metabolism of DL-Ins(1,3,4,5)P4 (10 microM) in these cells at 25 degrees C was investigated by h.p.l.c., substantial amounts of Ins(1,4,5)P3 (0.2 microM) and Ins(1,3,4)P3 (0.8 microM) were found to be produced within 3 min. Analysis of DL-Ins(1,3,4,5)P4 incubation with cells at 4 degrees C, however, indicated that metabolism had been arrested ([3H]Ins(1,4,5)P3 detection limits were estimated to be approx. 0.01 microM). When chemically synthesized DL-Ins(1,3,4,5)P4 and incubation conditions of low temperature were used, the Ca2(+)-releasing properties of this compound were established to be 1 microM and 19% for the EC50 and maximal response values respectively. The results obtained strongly suggest that Ins(1,3,4,5)P4 alone has the ability to release intracellular Ca2+. However, in the presence of sub-maximal concentrations of Ins(1,4,5)P3, Ca2+ release appears to be synergistic with Ins(1,3,4,5)P4, but at supramaximal concentrations not even additive effects are observed.

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