Plic-1, a new target in repressing epileptic seizure by regulation of GABAAR function in patients and a rat model of epilepsy

Zhang, Yujiao; Li, Zengyou; Gu, Juan; Zhang, Yanke; Wang, Wei; Shen, Hui; Chen, Guojun; Wang, Xuefeng

doi:10.1042/cs20150202

Cited by 20 publications

(35 citation statements)

References 48 publications

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“…The main hubs associated with the HS group were Cyb5d2 , Ubqln1 , Rc3h1 (greenyellow), Cml1 , Ralbp1 and Rab2b (pink), and Tma7 , Sumo2 , Apln and Foxm1 (turquoise). Among these genes, Ubqln1 ( Zhang et al, 2015 ) and Ralbp1 ( Bae et al, 2013 ) regulate seizure threshold via the GABAergic signaling. In parallel, Rab2b ( Ayala et al, 1990 ) and Foxm1 ( Ueno et al, 2008 ) play a role in neuronal differentiation.…”

Section: Resultsmentioning

confidence: 99%

Temporal analysis of hippocampal CA3 gene coexpression networks in a rat model of febrile seizures

Azevedo

Khaled

Santos

et al. 2018

Disease Models &Amp; Mechanisms

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Complex febrile seizures during infancy constitute an important risk factor for development of epilepsy. However, little is known about the alterations induced by febrile seizures that make the brain susceptible to epileptic activity. In this context, the use of animal models of hyperthermic seizures (HS) could allow the temporal analysis of brain molecular changes that arise after febrile seizures. Here, we investigated temporal changes in hippocampal gene coexpression networks during the development of rats submitted to HS. Total RNA samples were obtained from the ventral hippocampal CA3 region at four time points after HS at postnatal day (P) 11 and later used for gene expression profiling. Temporal endpoints were selected for investigating the acute (P12), latent (P30 and P60) and chronic (P120) stages of the HS model. A weighted gene coexpression network analysis was used to characterize modules of coexpressed genes, as these modules might contain genes with similar functions. The transcriptome analysis pipeline consisted of building gene coexpression networks, identifying network modules and hubs, performing gene-trait correlations and examining changes in module connectivity. Modules were functionally enriched to identify functions associated with HS. Our data showed that HS induce changes in developmental, cell adhesion and immune pathways, such as Wnt, Hippo, Notch, Jak-Stat and Mapk. Interestingly, modules involved in cell adhesion, neuronal differentiation and synaptic transmission were activated as early as 1 day after HS. These results suggest that HS trigger transcriptional alterations that could lead to persistent neurogenesis, tissue remodeling and inflammation in the CA3 hippocampus, making the brain prone to epileptic activity.

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Section: Resultsmentioning

confidence: 99%

Temporal analysis of hippocampal CA3 gene coexpression networks in a rat model of febrile seizures

Azevedo

Khaled

Santos

et al. 2018

Disease Models &Amp; Mechanisms

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“…The epileptic seizures were evaluated by Racine score [43]. Only convulsive seizures reached to the stage 4 or 5 were considered as being successfully kindled [44]. All rats were continuously monitored by a video recording system after injection of pilocarpine until they were sacrificed.…”

Section: Methodsmentioning

confidence: 99%

Nitrobenzylthioinosine mimics adenosine to attenuate the epileptiform discharge of hippocampal neurons from epileptic rats

et al. 2017

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Nitrobenzylthioinosine (NBTI), a specific inhibitor of type 1 equilibrative nucleoside transporter, could regulate the extracellular adenosine concentration and have protective roles in seizures. However, the protection mechanism of NBTI in seizures remains poorly understood. Here, the expression pattern and subcellular distribution of adenosine A1 receptor were detected by Western blot analysis and double-labeling immunofluorescence staining in Lithium Chloride-Pilocarpine induced epileptic rat model. At 24 h after pilocarpine induced rat seizures, hippocampal slices were prepared and the evoked excitatory postsynaptic currents (eEPSCs) amplitude of pyramidal neurons in hippocampus CA1 region was recorded using whole-cell patch clamp. In vivo, compared to control group, Western blotting analysis showed that the expression of adenosine A1 receptor protein was increased at 24 h and 72 h after seizure, didn't change at 0 min and 1 w, and decreased at 2 w. Double-label immunofluorescence revealed that adenosine A1 receptor was mainly expressed in the membrane and cytoplasm of neurons. In Vitro, adenosine decreased the eEPSCs amplitude of pyramidal neurons in hippocampus CA1 region, NBTI also had the same effect. Meantime, NBTI could further inhibit eEPSCs amplitude on the basis of lower concentration adenosine (50μM), and adenosine A1 receptor inhibitor DPCPX partially reversed this effect. Taken together, we confirmed that the expression of adenosine A1 receptor protein was increased in the early seizures and decreased in the late seizures. At the same time, NBTI mimics adenosine to attenuate the epileptiform discharge through adenosine A1 receptor, which might provide a novel therapeutic approach toward the control of epilepsy.

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“…UBQLN1 is lost and under-expressed in 50% of lung adenocarcinomas and loss of either UBQLN1 or UBQLN2 promotes epithelial to mesenchymal transition (EMT) in lung adenocarcinoma cell lines (11). Additionally, UBQLN1 is known to regulate other cell surface receptors like Presenilins (12), GABA A receptors (13,14) and nicotinic acetylcholine receptors (15). Here, we demonstrate that UBQLN1 interacts with IGF1R, IGF2R and INSR and is essential for normal expression and activity of IGF1R in lung adenocarcinoma cells.…”

Section: Introductionmentioning

confidence: 99%

Regulation of insulin-like growth factor receptors by Ubiquilin1

Kurlawala

Dunaway

Shah

et al. 2017

Biochemical Journal

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Insulin-like growth factor-1 receptor (IGF1R) is a receptor tyrosine kinase that mediates growth, proliferation and survival. Dysregulation of IGF pathway contributes to initiation, progression and metastasis of cancer and is also involved in diseases of glucose metabolism, such as Diabetes. We have identified Ubiquilin1 (UBQLN1) as a novel interaction partner of IGF1R, IGF2R and Insulin Receptor. UBQLN family of proteins have been studied primarily in the context of protein quality control and in the field of neurodegenerative disorders. Our laboratory discovered a link between UBQLN1 function and tumorigenesis, such that UBQLN1 is lost and under-expressed in 50% of human lung adenocarcinoma cases. We demonstrate here that UBQLN1 regulates expression and activity of IGF1R. Following loss of UBQLN1 in lung adenocarcinoma cells, there is accelerated loss of IGF1R. Despite decreased levels of total receptors, the ratio of active:total receptors is higher in cells that lack UBQLN1. UBQLN1 also regulates Insulin Receptor (INSR) and IGF2R post-stimulation with ligand. We conclude that UBQLN1 is essential for normal regulation of IGF receptors. UBQLN1 deficient cells demonstrate increased cell viability compared to control when serum starved and stimulation of IGF pathway in these cells increased their migratory potential by 3-fold. As the IGF pathway is involved in processes of normal growth, development, metabolism and cancer progression, understanding its regulation by Ubiquilin1 can be of tremendous value to many disciplines.

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Plic-1, a new target in repressing epileptic seizure by regulation of GABAAR function in patients and a rat model of epilepsy

Cited by 20 publications

References 48 publications

Temporal analysis of hippocampal CA3 gene coexpression networks in a rat model of febrile seizures

Temporal analysis of hippocampal CA3 gene coexpression networks in a rat model of febrile seizures

Nitrobenzylthioinosine mimics adenosine to attenuate the epileptiform discharge of hippocampal neurons from epileptic rats

Regulation of insulin-like growth factor receptors by Ubiquilin1

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