Transgenic overexpression of furin increases epileptic susceptibility

Yang, Yi; He, Mingzhu; Tian, Xin; Guo, Yi; Liu, Feng; Li, Yun; Zhang, Haiqing; Lu, Xi; Xu, Dan; Zhou, Ruijiao; Ma, Yuanlin; Wang, Wei; Chen, Guojun; Hu, Yun; Wang, Xuefeng

doi:10.1038/s41419-018-1076-x

Cited by 18 publications

(20 citation statements)

References 57 publications

(55 reference statements)

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“…Furin and other PCs process a large number of precursor proteins, such as hormones, neuropeptides, growth factors and their receptors, bacterial toxins, and adhesion molecule, through various secretory pathways (Seidah and Prat, 2012). Thus, the deregulation of FURIN is correlated with a variety of pathological conditions, including cardiovascular disease (Yakala et al, 2019), rheumatoid disease (Valli et al, 2019), endocrinopathies (Al Rifai et al, 2017), and central nervous system disorder (Yang et al, 2018). As for cancers, several studies have found that FURIN is expressed in various cancers and sarcomas (Khatib et al, 2002;Coppola et al, 2008;Lee et al, 2016;Jaaks and Bernasconi, 2017).…”

Section: Introductionmentioning

confidence: 99%

Pan-Cancer Analysis of FURIN as a Potential Prognostic and Immunological Biomarker

Zhou

Gao

2021

Front. Mol. Biosci.

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BackgroundFurin is a calcium-dependent protease that processes various precursor proteins through diverse secretory pathways. The deregulation of FURIN correlated with the prognosis of patients in numerous diseases. However, the role of FURIN in human pan-cancer is still largely unknown.MethodsMultiple bioinformatic methods were employed to comprehensively analyze the correlation of FURIN expression with prognosis, mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB), DNA methylation, tumor immune infiltration, and common immune checkpoint inhibitors (ICIs) from the public database, and aim to evaluate the potential prognostic value of FURIN across cancers.ResultsFURIN was aberrantly expressed and was strongly correlated with MMR, MSI, TMB, and DNA methylation in multiple types of cancer. Moreover, survival analysis across cancers revealed that FURIN expression was correlated with overall survival (OS) in four cancers, disease-specific survival (DSS) in five cancers, progression-free interval (PFI) in seven cancers, and disease-free interval (DFI) in two cancers. Also, FURIN expression was related to immune cell infiltration in 6 cancers and ImmuneScore/StromalScore in 10 cancers, respectively. In addition, FURIN expression also showed strong association between expression levels and immune checkpoint markers in three cancers.ConclusionFURIN can serve as a significant prognostic biomarker and correlate with tumor immunity in human pan-cancer.

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Section: Introductionmentioning

confidence: 99%

Pan-Cancer Analysis of FURIN as a Potential Prognostic and Immunological Biomarker

Zhou

Gao

2021

Front. Mol. Biosci.

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“…The method of sIPSCs recording was as same as mIPSCs without adding TTX in ACSF. sIPSCs were recorded in the present of gabazine (SR95531) (0.5 μ m ) or picrotoxin (10 μ m ) in ACSF 20 . eIPSCs were collected in the present of DNQX (20 μ m ) and APV (40 μ m ) at a holding potential of − 70 mV.…”

Section: Methodsmentioning

confidence: 99%

Protrudin modulates seizure activity through GABAA receptor regulation

Yang

Zhou

et al. 2019

Cell Death Dis

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Epilepsy is a serious neurological disease characterized by recurrent unprovoked seizures. The exact etiology of epilepsy is not fully understood. Protrudin is a neural membrane protein and is found to be mutated in hereditary spastic paraplegia that characterized by symptoms like seizures. Here, we reported that the expression of protrudin was downregulated in the temporal neocortex of epileptic patients and in the hippocampus and cortex of pentylenetetrazol and kainic acid-kindled epileptic mouse models. Behavioral and electroencephalogram analyses indicated that overexpression of protrudin in the mouse hippocampus increased the latency of the seizure and decreased the frequency and duration of seizure activity. Using whole-cell patch clamp, overexpression of protrudin in the mouse hippocampus resulted in a reduction in action potential frequency and an increase in gamma-aminobutyric acid (GABA)ergic inhibitory current amplitude. Moreover, western blot analysis showed that the membrane expression of the GABA A receptor β2/3 subunit was also upregulated after protrudin overexpression, and coimmunoprecipitation resulted in a protein–protein interaction between protrudin, GABAARβ2/3 and GABA receptor-associated protein in the hippocampus of epileptic mice. These findings suggest that protrudin probably inhibits the occurrence and development of epilepsy through the regulation of GABAA receptor-mediated synaptic transmission, and protrudin might be a promising target for the treatment of epilepsy.

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“…The mice in the PTZ-kindled model were intraperitoneally injected with a daily subconvulsive dose of PTZ (35 mg/kg, Sigma-Aldrich, USA) between 9:00 AM and 11:00 AM. 13,14 The rest mice were assigned as controls and were injected with the corresponding dose of saline solution. The intensity of seizure was evaluated on the basis of Racine's scale evaluation 13 : 1: mouse and facial movements; 2: head nodding; 3: forelimb clonus; 4: rearing; and 5: rearing and falling.…”

Section: Ptz-kindled Mouse Modelmentioning

confidence: 99%

“…Cultures of hippocampal neurons were prepared from postnatal day 0 C57BL/6J pups of either sex as mentioned. 14,15 Neurons were plated in DMEM containing 10% fetal bovine serum (FBS) (Scitecher, French), 1% penicillin-streptomycin (P/S) (Gibco, USA), and 1% lglutamine (Gbico, Brazil). Four to six hours later, the culture medium was exchanged completely with the neurobasal medium containing 2% B27 supplement (Gbico, USA), 1% P/S, and 1% l-glutamine.…”

Section: Neuronal Culture Preparation Dna Constructs and Transfectionmentioning

confidence: 99%

STK24 modulates excitatory synaptic transmission in epileptic hippocampal neurons

Yang

Jiang

et al. 2020

CNS Neurosci Ther

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Introduction A large amount of literature has indicated that excitatory synaptic transmission plays a crucial role in epilepsy, but the detailed pathogenesis still needs to be clarified. Methods In the present study, we used samples from patients with temporal lobe epilepsy, pentylenetetrazole‐kindled mice, and Mg 2+ ‐free‐induced epileptic cultured hippocampal neurons to detect the expression pattern of STK24. Then, the whole‐cell recording was carried out after STK24 overexpression in the Mg 2+ ‐free‐induced epileptic cultured hippocampal neurons. In addition, coimmunoprecipitation was performed to detect the association between endogenous STK24 and main subunits of NMDARs and AMPARs in the hippocampus of PTZ‐kindled mice. Results Here, we reported that STK24 was specifically located in epileptic neurons of human and pentylenetetrazole‐kindled mice. Meanwhile, the expression of STK24 was significantly down‐regulated in these samples which are mentioned above. Besides, we found that the amplitude of miniature excitatory postsynaptic currents was increased in STK24 overexpressed epileptic hippocampal cultured neurons, which means the excitatory synaptic transmission was changed. Moreover, the coimmunoprecipitation, which further supported the previous experiment, indicated an association between STK24 and the subunits of the NMDA receptor. Conclusion These findings expand our understanding of how STK24 involved in the excitatory synaptic transmission in epilepsy and lay a foundation for exploring the possibility of STK24 as a drug target.

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Transgenic overexpression of furin increases epileptic susceptibility

Cited by 18 publications

References 57 publications

Pan-Cancer Analysis of FURIN as a Potential Prognostic and Immunological Biomarker

Pan-Cancer Analysis of FURIN as a Potential Prognostic and Immunological Biomarker

Protrudin modulates seizure activity through GABAA receptor regulation

STK24 modulates excitatory synaptic transmission in epileptic hippocampal neurons

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