Lipids, Mitochondria and Cell Death: Implications in Neuro-oncology

Colquhoun, Alison

doi:10.1007/s12035-010-8134-4

Cited by 30 publications

(15 citation statements)

References 134 publications

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“…The mechanisms underlying ROS's biological functions are extremely complicated [36]. Identifying key molecules downstream ROS-mediated signaling pathways in cancer cells is required for improving the therapeutic effects of drugs or developing novel anticancer reagents [37, 38].…”

Section: Discussionmentioning

confidence: 99%

Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways

Liu

Chen

et al. 2014

Oxidative Medicine and Cellular Longevity

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Piperlongumine (PL) is recently found to kill cancer cells selectively and effectively via targeting reactive oxygen species (ROS) responses. To further explore the therapeutic effects of PL in cancers, we investigated the role and mechanisms of PL in cancer cell migration. PL effectively inhibited the migration of human glioma (LN229 or U87 MG) cells but not normal astrocytes in the scratch-wound culture model. PL did not alter EdU+-cells and cdc2, cdc25c, or cyclin D1 expression in our model. PL increased ROS (measured by DCFH-DA), reduced glutathione, activated p38 and JNK, increased IκBα, and suppressed NFκB in LN229 cells after scratching. All the biological effects of PL in scratched LN229 cells were completely abolished by the antioxidant N-acetyl-L-cysteine (NAC). Pharmacological administration of specific p38 (SB203580) or JNK (SP600125) inhibitors significantly reduced the inhibitory effects of PL on LN229 cell migration and NFκB activity in scratch-wound and/or transwell models. PL prevented the deformation of migrated LN229 cells while NAC, SB203580, or SP600125 reversed PL-induced morphological changes of migrated cells. These results suggest potential therapeutic effects of PL in the treatment and prevention of highly malignant tumors such as glioblastoma multiforme (GBM) in the brain by suppressing tumor invasion and metastasis.

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Section: Discussionmentioning

confidence: 99%

Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways

Liu

Chen

et al. 2014

Oxidative Medicine and Cellular Longevity

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“…These effects are likely related, since ROS can react rapidly with cellular macromolecules and induce mitochondrial damage (Puntel et al, 2010; Colquhoun, 2010; Forkink et al, 2010). Furthermore, because MeHg can cause a pronounced disruption of calcium homeostasis (Stavrovskaya and Kristal, 2010), it is plausible that alterations in Ca 2+ homeostasis could lead to the collapse of the inner mitochondrial membrane potential, as well as the opening of the mitochondrial permeability pore, events that ultimately result in the loss of mitochondrial function, ROS formation and cell death (Puntel et al, 2010; Colquhoun, 2010; Forkink et al, 2010). Thus, it is reasonable to assume that mitochondria are the primary molecular target for MeHg- and MeHg–Cys-induced cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Modulation of methylmercury uptake by methionine: Prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism

Roos

Puntel

Farina

et al. 2011

Toxicology and Applied Pharmacology

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Methylmercury (MeHg) is an ubiquitous environmental pollutant which is transported into the mammalian cells when present as the methylmercury-cysteine conjugate (MeHg–Cys). With special emphasis on hepatic cells, due to their particular propensity to accumulate an appreciable amount of Hg after exposure to MeHg, this study was performed to evaluate the effects of methionine (Met) on Hg uptake, reactive species (RS) formation, oxygen consumption and mitochondrial function/cellular viability in both liver slices and mitochondria isolated from these slices, after exposure to MeHg or the MeHg–Cys complex. The liver slices were pre-treated with Met (250 μM) 15 min before being exposed to MeHg (25 μM) or MeHg–Cys (25 μM each) for 30 min at 37 °C. The treatment with MeHg caused a significant increase in the Hg concentration in both liver slices and mitochondria isolated from liver slices. Moreover, the Hg uptake was higher in the group exposed to the MeHg–Cys complex. In the DCF (dichlorofluorescein) assay, the exposure to MeHg and MeHg–Cys produced a significant increase in DFC reactive species (DFC-RS) formation only in the mitochondria isolated from liver slices. As observed with Hg uptake, DFC-RS levels were significantly higher in the mitochondria treated with the MeHg–Cys complex compared to MeHg alone. MeHg exposure also caused a marked decrease in the oxygen consumption of liver slices when compared to the control group, and this effect was more pronounced in the liver slices treated with the MeHg–Cys complex. Similarly, the loss of mitochondrial activity/cell viability was greater in liver slices exposed to the MeHg–Cys complex when compared to slices treated only with MeHg. In all studied parameters, Met pre-treatment was effective in preventing the MeHg-and/or MeHg–Cys-induced toxicity in both liver slices and mitochondria. Part of the protection afforded by Met against MeHg may be related to a direct interaction with MeHg or to the competition of Met with the complex formed between MeHg and endogenous cysteine. In summary, our results show that Met pre-treatment produces pronounced protection against the toxic effects induced by MeHg and/or the MeHg–Cys complex on mitochondrial function and cell viability. Consequently, this amino acid offers considerable promise as a potential agent for treating acute MeHg exposure.

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“…The hydroxyl radical •OH is highly reactive and causes damage to nucleic acids and proteins, this radical also promotes lipid peroxidation [2, 12, 33]. Due to their high reactivity, hydroxyl radicals are especially harmful and considered a major cause of oxidant-induced damage [34].…”

Section: Introductionmentioning

confidence: 99%

Nuclear Transport: A Switch for the Oxidative Stress—Signaling Circuit?

Kodiha

Stochaj

2012

Journal of Signal Transduction

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Imbalances in the formation and clearance of reactive oxygen species (ROS) can lead to oxidative stress and subsequent changes that affect all aspects of physiology. To limit and repair the damage generated by ROS, cells have developed a multitude of responses. A hallmark of these responses is the activation of signaling pathways that modulate the function of downstream targets in different cellular locations. To this end, critical steps of the stress response that occur in the nucleus and cytoplasm have to be coordinated, which makes the proper communication between both compartments mandatory. Here, we discuss the interdependence of ROS-mediated signaling and the transport of macromolecules across the nuclear envelope. We highlight examples of oxidant-dependent nuclear trafficking and describe the impact of oxidative stress on the transport apparatus. Our paper concludes by proposing a cellular circuit of ROS-induced signaling, nuclear transport and repair.

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Lipids, Mitochondria and Cell Death: Implications in Neuro-oncology

Cited by 30 publications

References 134 publications

Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways

Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways

Modulation of methylmercury uptake by methionine: Prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism

Nuclear Transport: A Switch for the Oxidative Stress—Signaling Circuit?

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