Short-Term Hyperosmolality Pretreatment on Cells Can Reduce the Radiosensitivity via RVI and Akt1 Activation

Liu, Hu; Huang, Yijuan; Zhang, Wei; Sha, Zhilin; Li, Bailong; Yang, Yue; Liu, Wen; Zhang, Chao; Gao, Fu; Cai, Jianming

doi:10.1159/000356585

Cited by 3 publications

(1 citation statement)

References 31 publications

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“…There are many studies concerning the role of several genes in radio sensitivity such as BAG-1 (bcl-2 associated athanogene), RVI (regulatory volume increase), etc [55,56]. However, genes involved in RF-EMFs sensitivity were unclear.…”

Section: Discussionmentioning

confidence: 99%

8-oxoG DNA Glycosylase-1 Inhibition Sensitizes Neuro-2a Cells to Oxidative DNA Base Damage Induced by 900 MHz Radiofrequency Electromagnetic Radiation

Wang

Liu

et al. 2015

Cell Physiol Biochem

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Background/Aims: The purpose of this study was to explore the in vitro putative genotoxicity during exposure of Neuro-2a cells to radiofrequency electromagnetic fields (RF-EMFs) with or without silencing of 8-oxoG DNA glycosylase-1 (OGG1). Methods: Neuro-2a cells treated with or without OGG1 siRNA were exposed to 900 MHz Global System for Mobile Communication (GSM) Talk signals continuously at a specific absorption rate (SAR) of 0, 0.5, 1 or 2 W/kg for 24 h. DNA strand breakage and DNA base damage were measured by the alkaline comet assay and a modified comet assay using formamidopyrimidine DNA glycosylase (FPG), respectively. Reactive oxygen species (ROS) levels and cell viability were monitored using the non-fluorescent probe 2, 7-dichlorofluorescein diacetate (DCFH-DA) and CCK-8 assay. Results: Exposure to 900 MHz RF-EMFs with insufficient energy could induce oxidative DNA base damage in Neuro-2a cells. These increases were concomitant with similar increases in the generation of reactive oxygen species (ROS). Without OGG1 siRNA, 2 W/kg RF-EMFs induced oxidative DNA base damage in Neuro-2a cells. Interestingly, with OGG1 siRNA, RF-EMFs could cause DNA base damage in Neuro-2a cells as low as 1 W/kg. However, neither DNA strand breakage nor altered cell viability was observed. Conclusion: Even if further studies remain conducted we support the hypothesis that OGG1 is involved in the process of DNA base repair and may play a pivotal role in protecting DNA bases from RF-EMF induced oxidative damage.

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Section: Discussionmentioning

confidence: 99%

8-oxoG DNA Glycosylase-1 Inhibition Sensitizes Neuro-2a Cells to Oxidative DNA Base Damage Induced by 900 MHz Radiofrequency Electromagnetic Radiation

Wang

Liu

et al. 2015

Cell Physiol Biochem

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Enhanced Orai1 and STIM1 expression as well as store operated Ca2+ entry in therapy resistant ovary carcinoma cells

Schmidt

Liu

et al. 2014

Oncotarget

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Mechanisms underlying therapy resistance of tumor cells include protein kinase Akt. Putative Akt targets include store-operated Ca2+-entry (SOCE) accomplished by pore forming ion channel unit Orai1 and its regulator STIM1. We explored whether therapy resistant (A2780cis) differ from therapy sensitive (A2780) ovary carcinoma cells in Akt, Orai1, and STIM1 expression, Ca2+-signaling and cell survival following cisplatin (100μM) treatment. Transcript levels were quantified with RT-PCR, protein abundance with Western blotting, cytosolic Ca2+-activity ([Ca2+]i) with Fura-2-fluorescence, SOCE from increase of [Ca2+]i following Ca2+-readdition after Ca2+-store depletion, and apoptosis utilizing flow cytometry. Transcript levels of Orai1 and STIM1, protein expression of Orai1, STIM1, and phosphorylated Akt, as well as SOCE were significantly higher in A2780cis than A2780 cells. SOCE was decreased by Akt inhibitor III (SH-6, 10μM) in A2780cis but not A2780 cells and decreased in both cell lines by Orai1 inhibitor 2-aminoethoxydiphenyl borate (2-ABP, 50μM). Phosphatidylserine exposure and late apoptosis following cisplatin treatment were significantly lower in A2780cis than A2780 cells, a difference virtually abolished by SH-6 or 2-ABP. In conclusion, Orai1/STIM1 expression and function are increased in therapy resistant ovary carcinoma cells, a property at least in part due to enhanced Akt activity and contributing to therapy resistance in those cells.

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Exploring the role of macromolecular crowding and TNFR1 in cell volume control

Biswas,

Roy,

Jana

et al. 2024

eLife

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The excessive cosolute densities in the intracellular fluid create a physicochemical condition called macromolecular crowding (MMC). Intracellular MMC entropically maintains the biochemical thermodynamic equilibria by favouring associative reactions while hindering transport processes. Rapid cell volume shrinkage during extracellular hypertonicity elevates the MMC and disrupts the equilibria, potentially ushering cell death. Consequently, cells actively counter the hypertonic stress through regulatory volume increase (RVI) and restore the MMC homeostasis. Here, we establish fluorescence anisotropy of EGFP as a reliable tool for studying cellular MMC and explore the spatiotemporal dynamics of MMC during cell volume instabilities under multiple conditions. Our studies reveal that the actin cytoskeleton enforces spatially varying MMC levels inside adhered cells. Within cell populations, MMC is uncorrelated with nuclear DNA content but anti-correlated with the cell spread area. Although different cell lines have statistically similar MMC distributions, their responses to extracellular hypertonicity vary. The intensity of the extracellular hypertonicity determines a cell's ability for RVI, which correlates with Nuclear Factor Kappa Beta (NFkB) activation. Pharmacological inhibition and knockdown experiments reveal that Tumour Necrosis Factor Receptor 1 (TNFR1) initiates the hypertonicity induced NFkB signalling and RVI. At severe hypertonicities, the elevated MMC amplifies cytoplasmic microviscosity and hinders Receptor Interacting Protein Kinase 1 (RIPK1) recruitment at the TNFR1 complex, incapacitating the TNFR1-NFkB signalling and consequently, RVI. Together, our studies unveil the involvement of TNFR1-NFkB signalling in modulating RVI and demonstrate the pivotal role of MMC in determining cellular osmoadaptability.

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Short-Term Hyperosmolality Pretreatment on Cells Can Reduce the Radiosensitivity via RVI and Akt1 Activation

Cited by 3 publications

References 31 publications

8-oxoG DNA Glycosylase-1 Inhibition Sensitizes Neuro-2a Cells to Oxidative DNA Base Damage Induced by 900 MHz Radiofrequency Electromagnetic Radiation

8-oxoG DNA Glycosylase-1 Inhibition Sensitizes Neuro-2a Cells to Oxidative DNA Base Damage Induced by 900 MHz Radiofrequency Electromagnetic Radiation

Enhanced Orai1 and STIM1 expression as well as store operated Ca2+ entry in therapy resistant ovary carcinoma cells

Exploring the role of macromolecular crowding and TNFR1 in cell volume control

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