Paliperidone protects SK-N-SH cells against glutamate toxicity via Akt1/GSK3β signaling pathway

Lei Peng; Xingzhen Zhang; Xianping Cui; Dexiao Zhu; Jintao Wu; Dong Sun; Qingwei Yue; Zeyan Li; Haili Liu; Guibao Li; Jing zhang; Hongyan Xu; Fuchen Liu; Chengkun Qin; Mingfeng Li; Jinhao Sun

doi:10.1016/j.schres.2014.05.037

Paliperidone protects SK-N-SH cells against glutamate toxicity via Akt1/GSK3β signaling pathway

Lei Peng, Xingzhen Zhang, Xianping Cui, Dexiao Zhu, Jintao Wu, Dong Sun, Qingwei Yue, Zeyan Li, Haili Liu, Guibao Li, Jing zhang, Hongyan Xu, Fuchen Liu, Chengkun Qin, Mingfeng Li, Jinhao Sun

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Schizophrenia is a heterogeneous psychotic illness and its etiology remains poorly understood. Recent studies have suggested that neurodegeneration is a component of schizophrenia pathology and some atypical antipsychotics appear to slow progressive morphological brain changes. In addition, the atypical antipsychotics were reported to have a superior therapeutic efficacy in treating schizophrenia and have a low incidence of extrapyramidal side effects (EPS) compared to typical antipsychotics. However, the mechanisms of atypical antipsychotics in treating schizophrenia and the basis for differences in their clinical effects were still totally unknown. In the present study, we investigated whether paliperidone shows protective effects on SK-N-SH cells from cell toxicity induced by exposure to glutamate. We examined the effects of the drugs on cell viability (measured by MTT metabolism assay and lactate dehydrogenase (LDH) activity assay), apoptosis rate, ROS levels and gene expression and phosphorylation of Akt1 and GSK3β. The results showed that paliperidone significantly increases the cell viability by MTT and LDH assays (p<. 0.05), in contrast to the typical antipsychotic (haloperidol), which had little neuroprotective activity. Moreover, paliperidone retarded the glutamate-mediated promotion of ROS and the rate of apoptosis (p<. 0.05). In addition, paliperidone also effectively reversed glutamate-induced decreases of gene expression and phosphorylation of Akt1 and GSK3β (both p<. 0.05). Our results demonstrated that paliperidone could effectively protect SK-N-SH cells from glutamate-induced damages via Akt1/GSK3β signaling pathway.

Original language	English (US)
Pages (from-to)	120-127
Number of pages	8
Journal	Schizophrenia research
Volume	157
Issue number	1-3
DOIs	https://doi.org/10.1016/j.schres.2014.05.037
State	Published - Aug 2014
Externally published	Yes

Keywords

Glutamate
Paliperidone
Protection
SK-N-SH
Schizophrenia

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

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10.1016/j.schres.2014.05.037

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@article{8e654970eaf54804a4c1c932f079fb6b,

title = "Paliperidone protects SK-N-SH cells against glutamate toxicity via Akt1/GSK3β signaling pathway",

abstract = "Schizophrenia is a heterogeneous psychotic illness and its etiology remains poorly understood. Recent studies have suggested that neurodegeneration is a component of schizophrenia pathology and some atypical antipsychotics appear to slow progressive morphological brain changes. In addition, the atypical antipsychotics were reported to have a superior therapeutic efficacy in treating schizophrenia and have a low incidence of extrapyramidal side effects (EPS) compared to typical antipsychotics. However, the mechanisms of atypical antipsychotics in treating schizophrenia and the basis for differences in their clinical effects were still totally unknown. In the present study, we investigated whether paliperidone shows protective effects on SK-N-SH cells from cell toxicity induced by exposure to glutamate. We examined the effects of the drugs on cell viability (measured by MTT metabolism assay and lactate dehydrogenase (LDH) activity assay), apoptosis rate, ROS levels and gene expression and phosphorylation of Akt1 and GSK3β. The results showed that paliperidone significantly increases the cell viability by MTT and LDH assays (p<. 0.05), in contrast to the typical antipsychotic (haloperidol), which had little neuroprotective activity. Moreover, paliperidone retarded the glutamate-mediated promotion of ROS and the rate of apoptosis (p<. 0.05). In addition, paliperidone also effectively reversed glutamate-induced decreases of gene expression and phosphorylation of Akt1 and GSK3β (both p<. 0.05). Our results demonstrated that paliperidone could effectively protect SK-N-SH cells from glutamate-induced damages via Akt1/GSK3β signaling pathway.",

keywords = "Glutamate, Paliperidone, Protection, SK-N-SH, Schizophrenia",

author = "Lei Peng and Xingzhen Zhang and Xianping Cui and Dexiao Zhu and Jintao Wu and Dong Sun and Qingwei Yue and Zeyan Li and Haili Liu and Guibao Li and Jing zhang and Hongyan Xu and Fuchen Liu and Chengkun Qin and Mingfeng Li and Jinhao Sun",

note = "Funding Information: This study was supported by grants of the National Natural Science Foundation of China (No. 81071081 , No. 81371471 ), Natural Science Foundation of Shandong Province ( ZR2010HM051 and ZR2012HM026 ), and a grant of Shandong Provincial Science and Technology Development Plan ( 2011GSF11810 ). ",

year = "2014",

month = aug,

doi = "10.1016/j.schres.2014.05.037",

language = "English (US)",

volume = "157",

pages = "120--127",

journal = "Schizophrenia research",

issn = "0920-9964",

publisher = "Elsevier B.V.",

number = "1-3",

}

TY - JOUR

T1 - Paliperidone protects SK-N-SH cells against glutamate toxicity via Akt1/GSK3β signaling pathway

AU - Peng, Lei

AU - Zhang, Xingzhen

AU - Cui, Xianping

AU - Zhu, Dexiao

AU - Wu, Jintao

AU - Sun, Dong

AU - Yue, Qingwei

AU - Li, Zeyan

AU - Liu, Haili

AU - Li, Guibao

AU - zhang, Jing

AU - Xu, Hongyan

AU - Liu, Fuchen

AU - Qin, Chengkun

AU - Li, Mingfeng

AU - Sun, Jinhao

N1 - Funding Information: This study was supported by grants of the National Natural Science Foundation of China (No. 81071081 , No. 81371471 ), Natural Science Foundation of Shandong Province ( ZR2010HM051 and ZR2012HM026 ), and a grant of Shandong Provincial Science and Technology Development Plan ( 2011GSF11810 ).

PY - 2014/8

Y1 - 2014/8

N2 - Schizophrenia is a heterogeneous psychotic illness and its etiology remains poorly understood. Recent studies have suggested that neurodegeneration is a component of schizophrenia pathology and some atypical antipsychotics appear to slow progressive morphological brain changes. In addition, the atypical antipsychotics were reported to have a superior therapeutic efficacy in treating schizophrenia and have a low incidence of extrapyramidal side effects (EPS) compared to typical antipsychotics. However, the mechanisms of atypical antipsychotics in treating schizophrenia and the basis for differences in their clinical effects were still totally unknown. In the present study, we investigated whether paliperidone shows protective effects on SK-N-SH cells from cell toxicity induced by exposure to glutamate. We examined the effects of the drugs on cell viability (measured by MTT metabolism assay and lactate dehydrogenase (LDH) activity assay), apoptosis rate, ROS levels and gene expression and phosphorylation of Akt1 and GSK3β. The results showed that paliperidone significantly increases the cell viability by MTT and LDH assays (p<. 0.05), in contrast to the typical antipsychotic (haloperidol), which had little neuroprotective activity. Moreover, paliperidone retarded the glutamate-mediated promotion of ROS and the rate of apoptosis (p<. 0.05). In addition, paliperidone also effectively reversed glutamate-induced decreases of gene expression and phosphorylation of Akt1 and GSK3β (both p<. 0.05). Our results demonstrated that paliperidone could effectively protect SK-N-SH cells from glutamate-induced damages via Akt1/GSK3β signaling pathway.

AB - Schizophrenia is a heterogeneous psychotic illness and its etiology remains poorly understood. Recent studies have suggested that neurodegeneration is a component of schizophrenia pathology and some atypical antipsychotics appear to slow progressive morphological brain changes. In addition, the atypical antipsychotics were reported to have a superior therapeutic efficacy in treating schizophrenia and have a low incidence of extrapyramidal side effects (EPS) compared to typical antipsychotics. However, the mechanisms of atypical antipsychotics in treating schizophrenia and the basis for differences in their clinical effects were still totally unknown. In the present study, we investigated whether paliperidone shows protective effects on SK-N-SH cells from cell toxicity induced by exposure to glutamate. We examined the effects of the drugs on cell viability (measured by MTT metabolism assay and lactate dehydrogenase (LDH) activity assay), apoptosis rate, ROS levels and gene expression and phosphorylation of Akt1 and GSK3β. The results showed that paliperidone significantly increases the cell viability by MTT and LDH assays (p<. 0.05), in contrast to the typical antipsychotic (haloperidol), which had little neuroprotective activity. Moreover, paliperidone retarded the glutamate-mediated promotion of ROS and the rate of apoptosis (p<. 0.05). In addition, paliperidone also effectively reversed glutamate-induced decreases of gene expression and phosphorylation of Akt1 and GSK3β (both p<. 0.05). Our results demonstrated that paliperidone could effectively protect SK-N-SH cells from glutamate-induced damages via Akt1/GSK3β signaling pathway.

KW - Glutamate

KW - Paliperidone

KW - Protection

KW - SK-N-SH

KW - Schizophrenia

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U2 - 10.1016/j.schres.2014.05.037

DO - 10.1016/j.schres.2014.05.037

M3 - Article

C2 - 24962437

AN - SCOPUS:84904113182

SN - 0920-9964

VL - 157

SP - 120

EP - 127

JO - Schizophrenia research

JF - Schizophrenia research

IS - 1-3

ER -

Paliperidone protects SK-N-SH cells against glutamate toxicity via Akt1/GSK3β signaling pathway

Abstract

Keywords

ASJC Scopus subject areas

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