Phosphoinositide 3-Kinases Upregulate System xc− via Eukaryotic Initiation Factor 2α and Activating Transcription Factor 4 – A Pathway Active in Glioblastomas and Epilepsy

Lewerenz, Jan; Baxter, Paul; Kassubek, Rebecca; Albrecht, Philipp; Liefferinge, Joeri Van; Westhoff, Mike‐Andrew; Halatsch, Marc‐Eric; Karpel‐Massler, Georg; Meakin, Paul J.; Hayes, John D.; Aronica, Eleonora; Smolders, Ilse Julia; Ludolph, Albert C.; Methner, Axel; Conrad, Marcus; Massie, Ann; Hardingham, Giles E.; Maher, Pamela

doi:10.1089/ars.2013.5455

Cited by 60 publications

(65 citation statements)

References 75 publications

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“…A significant decrease of VGLUT1 protein was described in subfields with neuronal loss and a significant increase in the DG, marked by mossy fiber sprouting [33]. In our hippocampal homogenates from patients, diagnosed and classified as the classical form, Wyler grade 3 [17,37], the unaltered hippocampal VGLUT1 protein expression could be the result of increased VGLUT1 expression in the DG that compensates the more moderate loss of VGLUT1 in other hippocampal subregions.…”

Section: Discussionmentioning

confidence: 57%

“…All autopsies were performed within 12 h after death. There were no significant differences in sex distribution or age between the two groups (Supplementary Table S2 in [17]). Autopsy hippocampal tissue from controls and surgically resected hippocampal tissue from patients with TLE and HS were snap frozen in liquid nitrogen and stored at −80 • C, until further use in qPCR and western blotting experiments.…”

Section: Human Samplesmentioning

confidence: 95%

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Altered vesicular glutamate transporter expression in human temporal lobe epilepsy with hippocampal sclerosis

Liefferinge

Jensen

Albertini

et al. 2015

Neuroscience Letters

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Link to publication Citation for published version (APA):Van Liefferinge, J., Jensen, C. J., Albertini, G., Bentea, E., Demuyser, T., Merckx, E., ... Massie, A. (2015). Altered vesicular glutamate transporter expression in human temporal lobe epilepsy with hippocampal sclerosis. Neuroscience Letters, 590, 184-188. DOI: 10.1016/j.neulet.2015 General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Download date: 13 May 2018Neuroscience Letters 590 (2015) [184][185][186][187][188] Contents lists available at ScienceDirect Neuroscience Letters j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / n e u l e t h i g h l i g h t s• VGLUTs mRNA remains unaffected in human sclerotic hippocampus ILAE type1.• Unaltered total VGLUT1 protein level in hippocampus of human TLE with HS ILAE type1.• Decreased VGLUT2 protein expression in hippocampus of human TLE with HS ILAE type1.• Increased VGLUT3 protein expression in hippocampus of human TLE with HS ILAE type1. a b s t r a c t Vesicular glutamate transporters (VGLUTs) are responsible for loading glutamate into synaptic vesicles. Altered VGLUT protein expression has been suggested to affect quantal size and glutamate release under both physiological and pathological conditions. In this study, we investigated mRNA and protein expression levels of the three VGLUT subtypes in hippocampal tissue of patients suffering from temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS), International League Against Epilepsy type1 (ILAE type1) compared to autopsy controls, using quantitative polymerase chain reaction and semi-quantitative western blotting. mRNA expression levels of the VGLUTs are unaffected in hippocampal epileptic tissue compared to autopsy controls. At the protein level, VGLUT1 expression remains unaltered, while VGLUT2 is significantly decreased and VGLUT3 protein is significantly increased in hippocampal biopsies from TLE patients compared to controls. Our findings at the protein level can be explained by previously described histopathological changes observed in HS. a r t i c l e i n f oAlthough VGLUTs have been repeatedly investigated in distinct rodent epilepsy models, their expression levels were hitherto not fully unraveled in the most difficult-to-treat form of epilepsy: TLE with HS ILAE t...

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Section: Discussionmentioning

confidence: 57%

Section: Human Samplesmentioning

confidence: 95%

Altered vesicular glutamate transporter expression in human temporal lobe epilepsy with hippocampal sclerosis

Liefferinge

Jensen

Albertini

et al. 2015

Neuroscience Letters

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“…For example, ATF4 contributes to basal transcription from the Slc7a11 gene via a mechanism involving eIF2␣ and the amino acid response element (34, 58). ATF4 has also been implicated in the up-regulation of Slc7a11 gene transcription by excessive excitatory neuronal activity in cortical neurons (59). Moreover, ATF4 contributes to the induction of xCT mRNA transcription in response to amino acid deprivation or proteasome inhibition, in the latter case together with Nrf2 (34, 57).…”

Section: Discussionmentioning

confidence: 99%

Interleukin 1β Regulation of the System xc− Substrate-specific Subunit, xCT, in Primary Mouse Astrocytes Involves the RNA-binding Protein HuR

Shi

Hewett

et al. 2016

Journal of Biological Chemistry

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“…Because the activity of cystine uptake in WT MEF is too low to perform kinetic analyses, we used MEF in which xCT expression was manipulated. These cells stably express xCT in xCT KO MEF under the control of the strong synthetic CAG (chicken ␤-actin and CMV) promoter (25). The apparent K i value of cystathionine for cystine uptake was 0.23 Ϯ 0.04 mM.…”

Section: Resultsmentioning

confidence: 99%

“…Cell Culture-Mouse embryonic fibroblasts (MEF) isolated from wild-type and xCT-deficient mice (8) and xCT-overexpressing MEF (25) were cultured routinely in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 2-mercaptoethanol (50 M), insulin-transferrin-selenium A (Life Technologies, Inc.), penicillin (50 units/ml), and streptomycin (50 g/ml) at 37°C in 5% CO 2 and 95% air. The addition of 2-mercaptoethanol is necessary for xCT-deficient MEF to grow even under routine cell culture conditions (8,26).…”

Section: Reverse Transcription-pcr (Rt-pcr)-totalmentioning

confidence: 99%

Cystathionine Is a Novel Substrate of Cystine/Glutamate Transporter

Kobayashi

Sato

Kasakoshi

et al. 2015

Journal of Biological Chemistry

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Phosphoinositide 3-Kinases Upregulate System x_c⁻ via Eukaryotic Initiation Factor 2α and Activating Transcription Factor 4 – A Pathway Active in Glioblastomas and Epilepsy

Cited by 60 publications

References 75 publications

Altered vesicular glutamate transporter expression in human temporal lobe epilepsy with hippocampal sclerosis

Altered vesicular glutamate transporter expression in human temporal lobe epilepsy with hippocampal sclerosis

Interleukin 1β Regulation of the System xc− Substrate-specific Subunit, xCT, in Primary Mouse Astrocytes Involves the RNA-binding Protein HuR

Cystathionine Is a Novel Substrate of Cystine/Glutamate Transporter

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