Downregulation of signal transduction and STAT3 expression exacerbates oxidative stress mediated by NLRP3 inflammasome

Activated nucleotide binding to the oligonucleotide receptor protein 3 (NLRP3) inflammasome is possibly involved in the pathogenesis of Alzheimer's disease through oxidative stress and neurogenic inflammation. Low expression of the signal transducer and activator of transcription 3 (STAT3) gene...

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Main Authors: Hua Bai, Qi-Fang Zhang, Juan-Juan Duan, De-Jun Yu, Li-Jie Liu
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2018-01-01
Series:Neural Regeneration Research
Subjects:
Online Access:http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=12;spage=2147;epage=2155;aulast=Bai
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spelling doaj-c51805c969e2494fb9362b4e858a1d8f2020-11-25T03:49:14ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742018-01-0113122147215510.4103/1673-5374.241470Downregulation of signal transduction and STAT3 expression exacerbates oxidative stress mediated by NLRP3 inflammasomeHua BaiQi-Fang ZhangJuan-Juan DuanDe-Jun YuLi-Jie LiuActivated nucleotide binding to the oligonucleotide receptor protein 3 (NLRP3) inflammasome is possibly involved in the pathogenesis of Alzheimer's disease through oxidative stress and neurogenic inflammation. Low expression of the signal transducer and activator of transcription 3 (STAT3) gene may promote the occurrence of neurodegenerative diseases to some extent. To clarify the roles of the NLRP3 inflammasome and STAT3 expression in oxidative stress, (1) SHSY5Y cells were incubated with 1 mM H2O2 to induce oxidative stress injury, and the expression of human-cell-specific signal transduction, STAT3-shRNA silencing signal transduction and STAT3 were detected. Cells were pretreated with Ca2+ chelator BAPATA-AM (0.1 mM) for 30 minutes as a control. (2) Western blot assay was used to analyze the expression of caspase-1, NLRP3, signal transduction and STAT3. Enzyme-linked immunosorbent assay was used to analyze interleukin-1β levels. Flow cytometry was carried out to calculate the number of apoptotic cells. We found that H2O2 treatment activated NLRP3 inflammasomes and decreased phosphorylation of signal transduction and STAT3 serine 727. BAPTA-AM pretreatment abolished the H2O2-induced activation of NLRP3 inflammasomes, caspase-1 expression, interleukin-1β expression and apoptosis in SHSY5Y cells, and had no effect in cells with downregulated STAT3 expression by RNAi. The findings suggest that downregulation of signal transduction and STAT3 expression may enhance the oxidative stress mediated by NLRP3, which may not depend on the Ca2+ signaling pathway.http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=12;spage=2147;epage=2155;aulast=Bainerve regeneration; signal transducer and activator of transcription 3; calcium; caspase-1; nucleotide binding to the oligonucleotide receptor protein 3; inflammasome; hydrogen peroxide; Alzheimer′s disease; shRNA; SHSY5Y cells; neural regeneration
collection DOAJ
language English
format Article
sources DOAJ
author Hua Bai
Qi-Fang Zhang
Juan-Juan Duan
De-Jun Yu
Li-Jie Liu
spellingShingle Hua Bai
Qi-Fang Zhang
Juan-Juan Duan
De-Jun Yu
Li-Jie Liu
Downregulation of signal transduction and STAT3 expression exacerbates oxidative stress mediated by NLRP3 inflammasome
Neural Regeneration Research
nerve regeneration; signal transducer and activator of transcription 3; calcium; caspase-1; nucleotide binding to the oligonucleotide receptor protein 3; inflammasome; hydrogen peroxide; Alzheimer′s disease; shRNA; SHSY5Y cells; neural regeneration
author_facet Hua Bai
Qi-Fang Zhang
Juan-Juan Duan
De-Jun Yu
Li-Jie Liu
author_sort Hua Bai
title Downregulation of signal transduction and STAT3 expression exacerbates oxidative stress mediated by NLRP3 inflammasome
title_short Downregulation of signal transduction and STAT3 expression exacerbates oxidative stress mediated by NLRP3 inflammasome
title_full Downregulation of signal transduction and STAT3 expression exacerbates oxidative stress mediated by NLRP3 inflammasome
title_fullStr Downregulation of signal transduction and STAT3 expression exacerbates oxidative stress mediated by NLRP3 inflammasome
title_full_unstemmed Downregulation of signal transduction and STAT3 expression exacerbates oxidative stress mediated by NLRP3 inflammasome
title_sort downregulation of signal transduction and stat3 expression exacerbates oxidative stress mediated by nlrp3 inflammasome
publisher Wolters Kluwer Medknow Publications
series Neural Regeneration Research
issn 1673-5374
publishDate 2018-01-01
description Activated nucleotide binding to the oligonucleotide receptor protein 3 (NLRP3) inflammasome is possibly involved in the pathogenesis of Alzheimer's disease through oxidative stress and neurogenic inflammation. Low expression of the signal transducer and activator of transcription 3 (STAT3) gene may promote the occurrence of neurodegenerative diseases to some extent. To clarify the roles of the NLRP3 inflammasome and STAT3 expression in oxidative stress, (1) SHSY5Y cells were incubated with 1 mM H2O2 to induce oxidative stress injury, and the expression of human-cell-specific signal transduction, STAT3-shRNA silencing signal transduction and STAT3 were detected. Cells were pretreated with Ca2+ chelator BAPATA-AM (0.1 mM) for 30 minutes as a control. (2) Western blot assay was used to analyze the expression of caspase-1, NLRP3, signal transduction and STAT3. Enzyme-linked immunosorbent assay was used to analyze interleukin-1β levels. Flow cytometry was carried out to calculate the number of apoptotic cells. We found that H2O2 treatment activated NLRP3 inflammasomes and decreased phosphorylation of signal transduction and STAT3 serine 727. BAPTA-AM pretreatment abolished the H2O2-induced activation of NLRP3 inflammasomes, caspase-1 expression, interleukin-1β expression and apoptosis in SHSY5Y cells, and had no effect in cells with downregulated STAT3 expression by RNAi. The findings suggest that downregulation of signal transduction and STAT3 expression may enhance the oxidative stress mediated by NLRP3, which may not depend on the Ca2+ signaling pathway.
topic nerve regeneration; signal transducer and activator of transcription 3; calcium; caspase-1; nucleotide binding to the oligonucleotide receptor protein 3; inflammasome; hydrogen peroxide; Alzheimer′s disease; shRNA; SHSY5Y cells; neural regeneration
url http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=12;spage=2147;epage=2155;aulast=Bai
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AT qifangzhang downregulationofsignaltransductionandstat3expressionexacerbatesoxidativestressmediatedbynlrp3inflammasome
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AT dejunyu downregulationofsignaltransductionandstat3expressionexacerbatesoxidativestressmediatedbynlrp3inflammasome
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