Calcium plays a key role in paraoxon-induced apoptosis in EL4 cells by regulating both endoplasmic reticulum- and mitochondria-associated pathways

Li, Lan; Du, Yi; Ju, Furong; Ma, Shunxiang; Zhang, Shengxiang

doi:10.3109/15376516.2016.1156796

Cited by 4 publications

(1 citation statement)

References 47 publications

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“…These studies have revealed that at low noncholinergic doses (i.e. doses below the threshold required to inhibit acetylcholinesterase), organophosphates such as POX and MLT not only act as genotoxic agents but also affect several other biochemical pathways that are independent of cholinesterases inhibition (Aluigi, Guida, & Falugi, ; Angelini et al, ; Giri, Prasad, Giri, & Sharma, ; Kwong, ; Li, Du, Ju, Ma, & Zhang, ; Masoud, Vijayasarathy, Fernandez‐Cabezudo, Petroianu, & Saleh, ; Rush, Liu, Hjelmhaug, & Lobner, ; Saleh, Vijayasarathy, Fernandez‐Cabezudo, et al, ; Saleh, Vijayasarathy, Fernandez‐Cabezudo, Taleb, & Petroianu, ). Our studies have revealed that at noncholinergic doses both POX and MLT induce apoptosis in cultured EL4 T lymphocytes and L929 murine fibroblasts, respectively (Masoud et al, ; Saleh, Vijayasarathy, Fernandez‐Cabezudo, et al, ; Saleh, Vijayasarathy, Masoud, et al, ).…”

Section: Introductionmentioning

confidence: 99%

Protective effect of metoclopramide against organophosphate‐induced apoptosis in the murine skin fibroblast L929

Jaber

Petroianu

Rizvi

et al. 2017

J of Applied Toxicology

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This study was performed to evaluate the protective efficacy of metoclopramide (MCP) against the organophosphates paraoxon (POX)- and malathion (MLT)-induced apoptosis in the murine L929 skin fibroblasts. L929 cells were exposed to either POX (10 nm) or 1.0 μm MLT in the absence and presence of increased concentrations of MCP. The protective effect of MCP on these organophosphate-stimulated apoptotic events was evaluated by flow cytometry analysis after staining with annexin-V/propidium iodide, processing and activation of the executioner caspase-3, cleavage of the poly-ADP ribose polymerase, fragmentation of the nucleosomal DNA and disruption of the mitochondrial membrane potential (Δψ). Our results showed that increased doses of MCP alone (≥10 μm) did not induce apoptosis or activation of caspase-3. Pretreatment of the cells with MCP attenuated all the apoptotic events triggered by the organophosphate compounds in a dose-dependent manner reaching ~70-80% protection when they were preincubated at 1 and 5 μm of the drug before the addition of POX and MLT, respectively. Interestingly, MCP did not offer a significant protective effect against the cytotoxicity of tumor necrosis factor-α, cisplatinum, etoposide or paclitaxel, which stimulate apoptosis by various mechanisms, suggesting that the anti-apoptotic effect of the drug is specific to organophosphates. The strong and specific anti-apoptotic activity of subclinical doses of MCP against the cytotoxicity of organophosphate compounds suggests its potential clinical application in treating their poisoning.

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Section: Introductionmentioning

confidence: 99%

Protective effect of metoclopramide against organophosphate‐induced apoptosis in the murine skin fibroblast L929

Jaber

Petroianu

Rizvi

et al. 2017

J of Applied Toxicology

View full text Add to dashboard Cite

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Investigation of novel pyrazole carboxamides as new apoptosis inducers on neuronal cells in Helicoverpa zea

Ren

Yang

Jin

et al. 2018

Bioorganic & Medicinal Chemistry

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Enantioselective apoptosis and oxidative damage induced by individual isomers of profenofos in primary hippocampal neurons

Zhang

et al. 2017

Journal of Environmental Science and Health, Part B

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The purpose of this study was to investigate the apoptosis-related cytotoxic effects and molecular mechanisms of individual isomers of profenofos (PFF) on primary hippocampal neurons at 1.0 to 20 mg L. The cell viability and lactate dehydrogenase (LDH) efflux indicated that (-)-PFF exposure was associated with more toxic effects than (+)-PFF above the concentration of 5 mg L (P < 0.5). Flow cytometric results showed that the percentages of apoptotic cells incubated with 20 mg L (-)-PFF, (+)-PFF and rac-PFF for 24 h reached 23.4%, 9.2% and 14.2% (P < 0.01), respectively. Hippocampal neurons incubated with (-)-PFF, (+)-PFF and rac-PFF exhibited a dose-dependent accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) and a dose-dependent inhibition of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, implying that the defense system of the tests induces oxidative damage. A statistically significant difference was observed between the two enantiomers at 5 mg L and above. Moreover, the results showed that (-)-PFF exposure caused a significant loss in mitochondrial transmembrane potential (MMP), an upregulation of Ca and Bax protein expression, a downregulation of Bcl-2 protein expression, and the activation of caspase-3 and caspase-9 in a dose-dependent manner; (+)-PFF and rac-PFF exhibited these effects to a lesser degree. All results suggest that PFF induced apoptosis in rat hippocampal neurons via the mitochondria-mediated pathway, and oxidative stress is one of the factors of PFF-induced apoptosis. In addition, (-)-PFF appears to play an important role in oxidative stress and apoptosis, indicating that enantioselectivity should be considered when assessing ecotoxicological effects and health risks of chiral pesticides.

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Calcium plays a key role in paraoxon-induced apoptosis in EL4 cells by regulating both endoplasmic reticulum- and mitochondria-associated pathways

Abstract: Calcium played a key role in POX-induced apoptosis in EL4 cells by regulating both ER- and mitochondria-associated pathways. The cross-talk of ER- and mitochondria-associated pathways was accomplished through calcium signal.

Cited by 4 publications

References 47 publications

Protective effect of metoclopramide against organophosphate‐induced apoptosis in the murine skin fibroblast L929

Protective effect of metoclopramide against organophosphate‐induced apoptosis in the murine skin fibroblast L929

Investigation of novel pyrazole carboxamides as new apoptosis inducers on neuronal cells in Helicoverpa zea

Enantioselective apoptosis and oxidative damage induced by individual isomers of profenofos in primary hippocampal neurons

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