Partial Protection of PC12 Cells from Cellular Stress by Low-Dose Sodium Nitroprusside Pre-treatment

Varga, Judit; Bátor, Judit; Nádasdi, Gergő; Árvai, Zita; Schipp, Renáta; Szeberényi, József

doi:10.1007/s10571-015-0312-5

Cited by 3 publications

(2 citation statements)

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“…5) after anisomycin treatment. A similar paracrine stimulation by transmembrane TRAIL molecules presumably carried by extracellular vesicles was observed in PC12 cells exposed to nitrosative stress [69].…”

Section: Discussionsupporting

confidence: 68%

Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells

et al. 2017

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The bacterial antibiotic anisomycin is known to induce apoptosis by activating several mitogen-activated protein kinases and by inhibiting protein synthesis. In this study, the influence of p53 protein on the apoptosis-inducing effect of anisomycin was investigated. The effect of protein synthesis-inhibiting concentration of anisomycin on apoptotic events was analyzed using Western blot, DNA fragmentation, and cell viability assays in wild-type PC12 and in mutant p53 protein expressing p143p53PC12 cells. Anisomycin stimulated the main apoptotic pathways in both cell lines, but p143p53PC12 cells showed lower sensitivity to the drug than their wild-type counterparts. Anisomycin caused the activation of the main stress kinases, phosphorylation of the p53 protein and the eukaryotic initiation factor eIF2α, proteolytic cleavage of protein kinase R, Bid, caspase-9 and -3. Furthermore, anisomycin treatment led to the activation of TRAIL and caspase-8, two proteins involved in the extrinsic apoptotic pathway. All these changes were stronger and more sustained in wtPC12 cells. In the presence of the dominant inhibitory p53 protein, p53- dependent genes involved in the regulation of apoptosis may be less transcribed and this can lead to the decrease of apoptotic processes in p143p53PC12 cells.

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Section: Discussionsupporting

confidence: 68%

Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells

et al. 2017

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“…likely accounts for the high efficacy of SNP in the present study, affecting metabolic activity, proliferation, and viability of K1 cells, as well as the total antioxidant capacity of cells. However, anti-tumor effects were observed mainly at concentrations considered highly toxic in the literature [43].…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Oxidant Toxicity and Oxidative Stress in Human Papillary Thyroid Carcinoma Cells K1

et al. 2022

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Medical gas plasmas are of emerging interest in pre-clinical oncological research. Similar to an array of first-line chemotherapeutics and physics-based therapies already approved for clinical application, plasmas target the tumor redox state by generating a variety of highly reactive species eligible for local tumor treatments. Considering internal tumors with limited accessibility, medical gas plasmas help to enrich liquids with stable, low-dose oxidants ideal for intratumoral injection and lavage. Pre-clinical investigation of such liquids in numerous tumor entities and models in vitro and in vivo provided evidence of their clinical relevance, broadening the range of patients that could benefit from medical gas plasma therapy in the future. Likewise, the application of such liquids might be promising for recurrent BRAF(V600E) papillary thyroid carcinomas, resistant to adjuvant administration of radioiodine. From a redox biology point of view, studying redox-based approaches in thyroid carcinomas is particularly interesting, as they evolve in a highly oxidative environment requiring the capability to cope with large amounts of ROS/RNS. Knowledge on their behavior under different redox conditions is scarce. The present study aimed to clarify resistance, proliferative activity, and the oxidative stress response of human papillary thyroid cancer cells K1 after exposure to plasma-oxidized DMEM (oxDMEM). Cellular responses were also evaluated when treated with different dosages of hydrogen peroxide and the RNS donor sodium nitroprusside (SNP). Our findings outline plasma-oxidized liquids as a promising approach targeting BRAF(V600E) papillary thyroid carcinomas and extend current knowledge on the susceptibility of cells to undergo ROS/RNS-induced cell death.

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Sodium nitroprusside induces H‐Ras depalmitoylation and alters the cellular response to hypoxia in differentiated and undifferentiated PC12 cells

Goloshvili

Barbakadze

Mikeladze

2019

Cell Biochemistry & Function

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Ras‐GTPases regulate many central signalling pathways in the cell. Hypoxia induces nitrosative/oxidative stress and dysregulates Ras‐dependent downstream processes. H‐Ras possesses two cysteine residues (C181 and C184) in the C‐termini, which are palmitoylated once or twice. Palmitoylation is sufficient for promoting stable plasma membrane localization. We hypothesized that high concentrations of hypoxia‐formed nitric oxide could induce terminal cysteine S‐nitrosylation, followed by depalmitoylation and H‐Ras mislocalization. We investigated the action of a 100‐μM nitric oxide‐donor (sodium nitroprusside [SNP]) and a 100‐μM palmitoylation inhibitor (2‐bromopalmitate) on the distribution of membrane‐bound S‐nitrosylated and palmitoylated H‐Ras under hypoxic/normoxic conditions in undifferentiated/differentiated pheochromocytoma (PC12) cells. We found that under normoxic conditions, SNP increases membrane‐bound H‐Ras nitrosylation only in differentiated cells, whereas under hypoxic conditions, SNP stimulates H‐Ras nitrosylation in both differentiated and undifferentiated cells. SNP greatly decreases the palmitoylation of H‐Ras under hypoxic conditions in both undifferentiated and differentiated cells, while under normoxic conditions, the effect of SNP is more negligible. Furthermore, Western blot analyses have shown that SNP decreases ERK phosphorylation under hypoxic conditions, in parallel with an elevation in hypoxia‐induced factor activity and intracellular succinate concentration. We propose that high concentrations of hypoxia‐formed nitric oxide can nitrosylate H‐Ras terminal cysteines, which induce H‐Ras activity dysregulation and alter the cellular response to hypoxia.Significance of the studyTo our knowledge, these observations may be important for cancer prevention and therapy because cancer is one of the most prevalent disorders caused by the misregulation of Ras activity by a redox agent. Oncogenic activation of the H‐Ras gene has been found in a wide variety of neoplastic transformations, and thus, investigation of the redox regulation of H‐Ras activity is significant for cancer research as well.

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Partial Protection of PC12 Cells from Cellular Stress by Low-Dose Sodium Nitroprusside Pre-treatment

Cited by 3 publications

References 61 publications

Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells

Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells

Low-Dose Oxidant Toxicity and Oxidative Stress in Human Papillary Thyroid Carcinoma Cells K1

Sodium nitroprusside induces H‐Ras depalmitoylation and alters the cellular response to hypoxia in differentiated and undifferentiated PC12 cells

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