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Article: iTRAQ proteomics analysis reveals that PI3K is highly associated with bupivacaine-induced neurotoxicity pathways

TitleiTRAQ proteomics analysis reveals that PI3K is highly associated with bupivacaine-induced neurotoxicity pathways
Authors
Issue Date2016
PublisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.wiley-vch.de/home/proteomics
Citation
Proteomics, 2016, v. 16 n. 4, p. 564-575 How to Cite?
AbstractBupivacaine, a commonly used local anesthetic, has potential neurotoxicity through diverse signaling pathways. However, the key mechanism of bupivacaine-induced neurotoxicity remains unclear. Cultured human SH-SY5Y neuroblastoma cells were treated (bupivacaine) or untreated (control) with bupivacaine for 24 h. Compared to the control group, bupivacaine significantly increased cyto-inhibition, cellular reactive oxygen species, DNA damage, mitochondrial injury, apoptosis (increased TUNEL-positive cells, cleaved caspase 3, and Bcl-2/Bax), and activated autophagy (enhanced LC3II/LC3I ratio). To explore changes in protein expression and intercommunication among the pathways involved in bupivacaine-induced neurotoxicity, an 8-plex iTRAQ proteomic technique and bioinformatics analysis were performed. Compared to the control group, 241 differentially expressed proteins were identified, of which, 145 were up-regulated and 96 were down-regulated. Bioinformatics analysis of the cross-talk between the significant proteins with altered expression in bupivacaine-induced neurotoxicity indicated that phosphatidyl-3-kinase (PI3K) was the most frequently targeted protein in each of the interactions. We further confirmed these results by determining the downstream targets of the identified signaling pathways (PI3K, Akt, FoxO1, Erk, and JNK). In conclusion, our study demonstrated that PI3K may play a central role in contacting and regulating the signaling pathways that contribute to bupivacaine-induced neurotoxicity.
Persistent Identifierhttp://hdl.handle.net/10722/229104
ISSN
2015 Impact Factor: 4.079
2015 SCImago Journal Rankings: 1.476

 

DC FieldValueLanguage
dc.contributor.authorZhao, W-
dc.contributor.authorLiu, Z-
dc.contributor.authorYu, X-
dc.contributor.authorLai, L-
dc.contributor.authorLi, H-
dc.contributor.authorLiu, Z-
dc.contributor.authorLi, L-
dc.contributor.authorJiang, S-
dc.contributor.authorXia, Z-
dc.contributor.authorXu, S-
dc.date.accessioned2016-08-23T14:09:01Z-
dc.date.available2016-08-23T14:09:01Z-
dc.date.issued2016-
dc.identifier.citationProteomics, 2016, v. 16 n. 4, p. 564-575-
dc.identifier.issn1615-9853-
dc.identifier.urihttp://hdl.handle.net/10722/229104-
dc.description.abstractBupivacaine, a commonly used local anesthetic, has potential neurotoxicity through diverse signaling pathways. However, the key mechanism of bupivacaine-induced neurotoxicity remains unclear. Cultured human SH-SY5Y neuroblastoma cells were treated (bupivacaine) or untreated (control) with bupivacaine for 24 h. Compared to the control group, bupivacaine significantly increased cyto-inhibition, cellular reactive oxygen species, DNA damage, mitochondrial injury, apoptosis (increased TUNEL-positive cells, cleaved caspase 3, and Bcl-2/Bax), and activated autophagy (enhanced LC3II/LC3I ratio). To explore changes in protein expression and intercommunication among the pathways involved in bupivacaine-induced neurotoxicity, an 8-plex iTRAQ proteomic technique and bioinformatics analysis were performed. Compared to the control group, 241 differentially expressed proteins were identified, of which, 145 were up-regulated and 96 were down-regulated. Bioinformatics analysis of the cross-talk between the significant proteins with altered expression in bupivacaine-induced neurotoxicity indicated that phosphatidyl-3-kinase (PI3K) was the most frequently targeted protein in each of the interactions. We further confirmed these results by determining the downstream targets of the identified signaling pathways (PI3K, Akt, FoxO1, Erk, and JNK). In conclusion, our study demonstrated that PI3K may play a central role in contacting and regulating the signaling pathways that contribute to bupivacaine-induced neurotoxicity.-
dc.languageeng-
dc.publisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.wiley-vch.de/home/proteomics-
dc.relation.ispartofProteomics-
dc.rightsThis is the accepted version of the following article: Proteomics, 2016, v. 16 n. 4, p. 564-575, which has been published in final form at http://onlinelibrary.wiley.com/wol1/doi/10.1002/pmic.201500202/abstract-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleiTRAQ proteomics analysis reveals that PI3K is highly associated with bupivacaine-induced neurotoxicity pathways-
dc.typeArticle-
dc.identifier.emailLi, H: lihaobo@hku.hk-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityXia, Z=rp00532-
dc.description.naturepostprint-
dc.identifier.doi10.1002/pmic.201500202-
dc.identifier.pmid26621341-
dc.identifier.hkuros261663-
dc.identifier.volume16-
dc.identifier.issue4-
dc.identifier.spage564-
dc.identifier.epage575-
dc.publisher.placeGermany-

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