Iron-induced oxidative stress activates AKT and ERK1/2 and decreases Dyrk1B and PRMT1 in neuroblastoma SH-SY5Y cells

Bautista, Elizabeth; Vergara, Paula; Segovia, José

doi:10.1016/j.jtemb.2015.11.005

Cited by 30 publications

(20 citation statements)

References 64 publications

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“…Although the literature is very sparse regarding the impact of iron on AKT signaling in intestinal cells, investigations conducted in other cell types can provide insight about its known effects. Studies conducted in neuroblastomas, hepatic macrophages, cerebral cortex synaptic endings and neurons, show that iron administration increases AKT activity in response to OxS [99][100][101][102]. Similar to our results, neurons exposed to iron display increased lipid peroxidation without alteration of cellular viability [103].…”

Section: Discussionsupporting

confidence: 90%

Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells

et al. 2020

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Background. Metabolic Syndrome (MetS), a major worldwide concern for the public health system, refers to a cluster of key metabolic components, and represents a risk factor for diabetes and cardiovascular diseases. As oxidative stress (OxS) and inflammation are the major triggers of insulin sensitivity (IS), a cardinal MetS feature, the principal aim of the present work is to determine whether glycomacropeptide (GMP), a milk-derived bioactive peptide, exerts beneficial effects on their expression. Methods. Fully differentiated intestinal Caco-2/15 cells are used to evaluate the preventive action of 2 mg/mL GMP against OxS and inflammation induced by the mixture iron-ascorbate (Fe/Asc) (200 μM:2 mM). The potency of GMP of decreasing the production of lipoproteins, including chylomicrons (CM), very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) is also assessed. Results. The administration of GMP significantly reduces malondialdehyde, a biomarker of lipid peroxidation, and raises superoxide dismutase 2 and glutathione peroxidase via the induction of the nuclear factor erythroid 2–related factor 2, a transcription factor, which orchestrates cellular antioxidant defenses. Similarly, GMP markedly lowers the inflammatory agents tumor necrosis factor-α and cyclooxygenase-2 via abrogation of the nuclear transcription factor-kB. Moreover, GMP-treated cells show a down-regulation of Fe/Asc-induced mitogen activated protein kinase pathway, suggesting greater IS. Finally, GMP decreases the production of CM, VLDL, and LDL. Conclusions. Our results highlight the effectiveness of GMP in attenuating OxS, inflammation and lipoprotein biogenesis, as well as improving IS, the key components of MetS. Further investigation is needed to elucidate the mechanisms mediating the preventive action of GMP.

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Section: Discussionsupporting

confidence: 90%

Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells

et al. 2020

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“…High levels of Dyrk1B in arrested NIH3T3 cells have been reported (Deng, Mercer, Shah, Ewton, & Friedman, ), which is in agreement with our results; and in 2009 the same group demonstrated that Dyrk1B maintains the viability of pancreatic cancer cells by reducing reactive oxygen species (ROS) (Deng, Ewton, & Friedman, ). Recently, we observed decreased Dyrk1B expression during iron‐induced neural cell death, indicating increased cellular vulnerability to oxidative stress (Bautista, Vergara, & Segovia, ). Moreover, it has been observed that Dyrk1B phosphorylates and destabilizes cyclin D1 and D3, which is essential for ubiquitination and degradation in the proteasome and, for keeping cells arrested (Zou, Ewton, Deng, Mercer, & Friedman, ).…”

Section: Discussionmentioning

confidence: 92%

Annexin A1, Annexin A2, and Dyrk 1B are upregulated during GAS1‐induced cell cycle arrest

Pérez‐Sánchez¹,

Jiménez²,

Quezada-Ramírez³

et al. 2017

Journal Cellular Physiology

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GAS1 is a pleiotropic protein that has been investigated because of its ability to induce cell proliferation, cell arrest, and apoptosis, depending on the cellular or the physiological context in which it is expressed. At this point, we have information about the molecular mechanisms by which GAS1 induces proliferation and apoptosis; but very few studies have been focused on elucidating the mechanisms by which GAS1 induces cell arrest. With the aim of expanding our knowledge on this subject, we first focused our research on finding proteins that were preferentially expressed in cells arrested by serum deprivation. By using a proteomics approach and mass spectrometry analysis, we identified 17 proteins in the 2-DE protein profile of serum deprived NIH3T3 cells. Among them, Annexin A1 (Anxa1), Annexin A2 (Anxa2), dual specificity tyrosine-phosphorylation-regulated kinase 1B (Dyrk1B), and Eukaryotic translation initiation factor 3, F (eIf3f) were upregulated at transcriptional the level in proliferative NIH3T3 cells. Moreover, we demonstrated that Anxa1, Anxa2, and Dyrk1b are upregulated at both the transcriptional and translational levels by the overexpression of GAS1. Thus, our results suggest that the upregulation of Anxa1, Anxa2, and Dyrk1b could be related to the ability of GAS1 to induce cell arrest and maintain cell viability. Finally, we provided further evidence showing that GAS1 through Dyrk 1B leads not only to the arrest of NIH3T3 cells but also maintains cell viability.

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“…Furthermore, the hyperphosphorylation of tau may not affect the interaction between tau and Fe 3+ , but Thr phosphorylation can modulate interactions between Fe 2+ and tau (Ahmadi et al, 2017 ), which may explain why previous studies have speculated no interaction between Fe and tau. As noted earlier, tau hyperphosphorylation is one of the key steps in NFT formation and it can be modulated by iron through the aberrant activation of tau kinases such as GSK3ß, CDK-5 and MAPK (Egaña et al, 2003 ; Lovell et al, 2004 ; Muñoz et al, 2006 ; Bautista et al, 2016 ). Though there is debate that this process may not be the primary cause of aggregation, as hyperphosphorylated tau is evident during animal hibernation and anesthesia-induced hypothermia (Arendt et al, 2003 ; Planel et al, 2007 ), the evidence suggests that iron may act as a co-factor for tau aggregation and the phosphorylated state of tau may induce conformational changes of the protein to mediate tau:iron interactions.…”

Section: Tau Pathologymentioning

confidence: 98%

Untangling Tau and Iron: Exploring the Interaction Between Iron and Tau in Neurodegeneration

Rao

Adlard

2018

Front. Mol. Neurosci.

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There is an emerging link between the accumulation of iron in the brain and abnormal tau pathology in a number of neurodegenerative disorders, such as Alzheimer’s disease (AD). Studies have demonstrated that iron can regulate tau phosphorylation by inducing the activity of multiple kinases that promote tau hyperphosphorylation and potentially also by impacting protein phosphatase 2A activity. Iron is also reported to induce the aggregation of hyperphosphorylated tau, possibly through a direct interaction via a putative iron binding motif in the tau protein, facilitating the formation of neurofibrillary tangles (NFTs). Furthermore, in human studies high levels of iron have been reported to co-localize with tau in NFT-bearing neurons. These data, together with our own work showing that tau has a role in mediating cellular iron efflux, provide evidence supporting a critical tau:iron interaction that may impact both the symptomatic presentation and the progression of disease. Importantly, this may also have relevance for therapeutic directions, and indeed, the use of iron chelators such as deferiprone and deferoxamine have been reported to alleviate the phenotypes, reduce phosphorylated tau levels and stabilize iron regulation in various animal models. As these compounds are also moving towards clinical translation, then it is imperative that we understand the intersection between iron and tau in neurodegeneration. In this article, we provide an overview of the key pathological and biochemical interactions between tau and iron. We also review the role of iron and tau in disease pathology and the potential of metal-based therapies for tauopathies.

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Iron-induced oxidative stress activates AKT and ERK1/2 and decreases Dyrk1B and PRMT1 in neuroblastoma SH-SY5Y cells

Cited by 30 publications

References 64 publications

Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells

Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells

Annexin A1, Annexin A2, and Dyrk 1B are upregulated during GAS1‐induced cell cycle arrest

Untangling Tau and Iron: Exploring the Interaction Between Iron and Tau in Neurodegeneration

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