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

1990 ◽  
Vol 272 (2) ◽  
pp. 519-524 ◽  
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.

scholarly journals Interactions between inositol tris- and tetrakis-phosphates. Effects on intracellular Ca2+ mobilization in SH-SY5Y cells

1991 ◽  
Vol 276 (1) ◽  
pp. 163-167 ◽  
Author(s):  
D J Gawler ◽  
B V L Potter ◽  
R Gigg ◽  
S R Nahorski
Keyword(s):  
Neuroblastoma Cells ◽  
Effective Concentration ◽  
Maximal Response ◽  
Maximal Effect ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Naturally Occurring ◽  
Inositol Tetrakisphosphate

The potential Ca2(+)-releasing activity of the inositol tetrakisphosphates Ins(1,3,4,6)P4 and DL-Ins(1,4,5,6)P4 and the inositol pentakisphosphate Ins(1,3,4,5,6)P5 and their effect on Ins(1,4,5)P3- and DL-Ins (1,3,4,5)P4-mediated Ca2+ release were examined in permeabilized SH-SY5Y human neuroblastoma cells. Neither DL-Ins(1,4,5,6)P4 nor Ins(1,3,4,5,6)P5 exhibit Ca2(+)-releasing activity at concentrations up to 10 microM, but Ins(1,3,4,6)P4 releases Ca2+ dose-dependently, with an EC50 value (conen, giving half-maximal effect) of 5.92 +/- 0.47 microM. Maximal response by this tetrakisphosphate (49 +/- 2.5%) is significantly less than that seen with Ins(1,4,5)P3 (60 +/- 3%) and is achieved at a concentration of 30 microM. In the presence of this concentration of Ins(1,3,4,6)P4 the EC50 value for Ins(1,4,5)P3-mediated Ca2+ release increases from 0.12 +/- 0.02 microM to 2.11 +/- 0.51 microM, providing evidence that this naturally occurring inositol tetrakisphosphate may recognize and exhibit its Ca2(+)-releasing activity via the Ins(1,4,5)P3 receptor. DL-Ins(1,3,4,5)P4, however, at its maximally effective concentration (10 microM) does not significantly affect Ins(1,4,5)P3-mediated Ca2+ release, and therefore appears to mediate its Ca2(+)-mobilizing action through a receptor distinct from that for Ins(1,4,5)P3.

scholarly journals Coupling of muscarinic receptors to the mobilization of intracellular Ca2+ stores in permeabilized SH-SY5Y human neuroblastoma cells

1990 ◽  
Vol 272 (1) ◽  
pp. 269-272 ◽  
Author(s):  
R J H Wojcikiewicz ◽  
S T Safrany ◽  
R A J Challiss ◽  
J Strupish ◽  
S R Nahorski
Keyword(s):  
Muscarinic Receptors ◽  
Neuroblastoma Cells ◽  
Dose Dependence ◽  
Maximal Response ◽  
Functional Coupling ◽  
Maximal Effect ◽  
Human Neuroblastoma Cells ◽  
Response Curves ◽  
Human Neuroblastoma ◽  
Intact Cells

Intracellular stores of Ca2+ were mobilized transiently by carbachol in suspensions of electrically permeabilized SH-SY5Y cells. The kinetics and the dose-dependence of this mobilization paralleled carbachol-induced increases in inositol 1,4,5-trisphosphate (InsP3) mass [for both parameters EC50 (concn. giving half-maximal response) = 60-70 microM]. Guanosine 5′-[gamma-thio]triphosphate enhanced the maximal effect and the potency of carbachol on Ca2+ mobilization and InsP3 mass, but caused separation of the dose-response curves (EC50 = 0.6 microM and 5.6 microM respectively). These data show that functional coupling of muscarinic receptors to Ca2+ mobilization can be maintained after permeabilization, reveal major effects of guanine nucleotides on agonist-induced Ca2+ mobilization and provide a basis for explanation of discrepancies between agonist potency on InsP3 concentration and Ca2+ mobilization in intact cells.

Differential Toxicity of 6-Hydroxydopamine in SH-SY5Y Human Neuroblastoma Cells and Rat Brain Mitochondria: Protective Role of Catalase and Superoxide Dismutase

2012 ◽  
Vol 37 (10) ◽  
pp. 2150-2160 ◽  
Author(s):  
Javier Iglesias-González ◽  
Sofía Sánchez-Iglesias ◽  
Estefanía Méndez-Álvarez ◽  
Sarah Rose ◽  
Atsuko Hikima ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Rat Brain ◽  
Neuroblastoma Cells ◽  
Brain Mitochondria ◽  
Protective Role ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Differential Toxicity ◽  
6 Hydroxydopamine

scholarly journals 4-Hydroxychalcone Induces Cell Death via Oxidative Stress in MYCN-Amplified Human Neuroblastoma Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Eszter Tuboly ◽  
Shane V. Hegarty ◽  
Cathal M. McCarthy ◽  
Aideen M. Sullivan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cytotoxic Effect ◽  
Neuroblastoma Cells ◽  
Reactive Oxygen ◽  
Prognostic Indicator ◽  
Oxygen Species ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.

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