Chelation of Extracellular Calcium-Induced Cell Death was Prevented by Glycogen Synthase Kinase-3 Inhibitors in PC12 Cells

Takadera, Tsuneo; Ohtsuka, Megumi; Aoki, Hiroaki

doi:10.1007/s10571-009-9442-y

Cited by 8 publications

(5 citation statements)

References 26 publications

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“…Assumingly the extracellular free Calcium concentration is approximately same to the serum free Calcium, which is about 1.2 μM, but this is still remain unclear. However, fluctuations of this value Increased levels of extracellular Calcium in the RB group treated with NK cells are in line with the study byTakadera, et al, (2010) concerning the chelation of extracellular Calcium with EGTA.…”

supporting

confidence: 89%

Detection of the Calcium and ATP Role in Apoptosis of Retinoblastoma Culture Cells through Caspase-3 Expression

Soebagjo¹,

Fatmariyanti²,

Sugianto³

et al. 2019

Rese. Jour. of Pharm. and Technol.

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Retinoblastoma is a malignant retinal tumor associated with apoptotic deregulation. Retinoblastoma cells are sensitive to NK cells. These cells can stimulate apoptosis. Apoptosis in retinoblastoma occurs in the early phase and is paradoxical. The increasing amounts of Bcl-2 and Caspase-3 as apoptotic executors are inversely proportional to apoptosis. Calcium and ATP as second messengers and signaling molecules play role in mediating cell responses including retinoblastoma cell development and death. Apoptosis requires sufficient energy from ATP and its mediated by Calcium. This study aimed to perceive the effects of Calcium and ATP in the process of retinoblastoma cell death through Caspase-3 pathway. The subjects were poorly differentiated retinoblastoma cell cultures treated with NK cells (treatment group) compared to those which were not exposed to NK cells (control group). Through the cell flowcytometry test that expresses Caspase-3 and apoptosis is calculated, meanwhile the levels of Calcium and ATP activity produced during the apoptosis process are quantitatively calculated. Examination of ATP activity uses a colorimetric method while the calcium content is calculated using a clinical chemistry system. Calcium and ATP were negatively correlated at 27.4% (p <0.05). ATP also showed a very significant negative correlation of 75.8% (p <0.01) against Caspase-3 and is significantly positively correlated with apoptosis of 46.8% (p,0.05). Whereas Caspase-3 is negatively correlated with apoptosis by 46.6% (p <0.05). In the Caspase-3 pathway, allogeneic NK cell administration in retinoblastoma cells increases the level of Calcium which plays a role in the early phase apoptosis process, whereas ATP which was formed is insufficient to cause maximal apoptosis due to extracellular calcium entry into NK cells. Extracellular ATP does not play a role in the induction of apoptosis in retinoblastoma cells treated with NK cells.

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supporting

confidence: 89%

Detection of the Calcium and ATP Role in Apoptosis of Retinoblastoma Culture Cells through Caspase-3 Expression

Soebagjo¹,

Fatmariyanti²,

Sugianto³

et al. 2019

Rese. Jour. of Pharm. and Technol.

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“…(Deniaud et al, 2008). This effect of BAPTA-AM was highly significant even though this drug has a modest effect on ROS levels in control cells in control group (Ahluwalia et al, 2001 ; Takadera et al, 2010). …”

Section: Discussionmentioning

confidence: 90%

Hyperglycemia magnifies Schwann cell dysfunction and cell death triggered by PA-induced lipotoxicity

et al. 2011

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Lipid overload resulting in lipotoxicity is prominent in a number of chronic diseases and has been associated with cellular dysfunction and cell death. This study characterizes palmitic acid-induced lipotoxicity (PA-LTx) in Schwann cell cultures grown in normal and high glucose concentrations. The study shows for the first time that Schwann cell (SC) cultures exposed to elevated levels of PA exhibit a dose and time –dependent loss in cell viability. Hoescht and Annexin V/7AAD staining confirmed cell death through apoptosis and the lipotoxic effect was more dramatic in SC cultures grown under high glucose conditions. The first indication of cellular dysfunction in treated SC cultures was a decrease in Ca++ levels in the endoplasmic reticulum (ER, [Ca++]ER) observed five minutes following the initial challenge with PA. This decrease in [Ca++]ER was followed by a significant increase in the expression of ER stress signature genes CHOP, Xbp1 and GRP78. The early ER stress response induced by PA-LTx was followed by a strong mitochondrial membrane depolarization. Flow cytometry using 2’, 7’-dichlorodihydrofluorescein diacetate (H2DCF-DA) showed an increase in oxidative stress within three to six hours after PA treatment. Treatment of cultures undergoing PA-LTx with the calcium chelator BAPTA-AM and the antioxidant MC1-186 significantly reversed the lipotoxic effect by decreasing the generation of ROS and significantly increasing cell viability. We conclude that lipotoxicity in Schwann cells results in cellular dysfunction and cell death that involves a robust ER stress response, mitochondrial dysfunction and an augmented stated of cellular oxidative stress (ASCOS).

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“…It will be important to determine which kinase inhibition profile correlates best with the ability to increase SMN and to use that information as part of a chemical optimization campaign to maximize the beneficial effects of using these compounds therapeutically (for example, there are some negative activities associated with alsterpaullone addition to Jurkat cells) 49 . It is also interesting to note that GSK-3 has been shown to have anti-apoptotic effects on different neuronal populations 50 . Determining whether any part of the survival promoting effect that GSK-3 inhibitors have on motor neurons is independent of SMN levels is essential (although we did not find that they enhanced motor neuron survival in general under the conditions of our experiment), as is investigating whether some of the pro-survival effects on other neurons might, unexpectedly, be modulated, in part, by increased SMN levels.…”

Section: Discussionmentioning

confidence: 99%

A screen for regulators of survival of motor neuron protein levels

et al. 2011

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The motor neuron disease Spinal Muscular Atrophy (SMA) results from mutations that lead to low levels of the ubiquitously expressed protein Survival of Motor Neuron (SMN). Ever-increasing data suggest that therapeutics that elevate SMN may be effective in treating SMA. We executed an image-based screen of annotated chemical libraries and discovered multiple classes of compounds that were able to increase cellular SMN. Among the most important was the RTK/PI3K/AKT/GSK-3 signaling cascade. Chemical inhibitors of GSK-3, as well as shRNAs directed against this target, elevate SMN levels primarily by stabilizing the protein. Of particular significance is that GSK-3 chemical inhibitors were also effective in motor neurons, not only in elevating SMN levels, but also in blocking the death that was produced when SMN was acutely reduced by a SMN-specific shRNA. Thus, we have established a screen capable of detecting drug-like compounds that correct the main phenotypic change that underlies SMA.

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Chelation of Extracellular Calcium-Induced Cell Death was Prevented by Glycogen Synthase Kinase-3 Inhibitors in PC12 Cells

Cited by 8 publications

References 26 publications

Detection of the Calcium and ATP Role in Apoptosis of Retinoblastoma Culture Cells through Caspase-3 Expression

Detection of the Calcium and ATP Role in Apoptosis of Retinoblastoma Culture Cells through Caspase-3 Expression

Hyperglycemia magnifies Schwann cell dysfunction and cell death triggered by PA-induced lipotoxicity

A screen for regulators of survival of motor neuron protein levels

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