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Features and mechanisms of propofol-induced protein kinase C (PKC) translocation and activation in living cells
Background and purpose: In this study, we aimed to elucidate the action mechanisms of propofol, particularly those underlying propofol-induced protein kinase C (PKC) translocation. Experimental approach: Various PKCs fused with green fluorescent protein (PKC-GFP) or other GFP-fused proteins were exp...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662334/ https://www.ncbi.nlm.nih.gov/pubmed/38026993 http://dx.doi.org/10.3389/fphar.2023.1284586 |
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author | Noguchi, Soma Kajimoto, Taketoshi Kumamoto, Takuya Shingai, Masashi Narasaki, Soshi Urabe, Tomoaki Imamura, Serika Harada, Kana Hide, Izumi Tanaka, Sigeru Yanase, Yuhki Nakamura, Shun-Ichi Tsutsumi, Yasuo M. Sakai, Norio |
author_facet | Noguchi, Soma Kajimoto, Taketoshi Kumamoto, Takuya Shingai, Masashi Narasaki, Soshi Urabe, Tomoaki Imamura, Serika Harada, Kana Hide, Izumi Tanaka, Sigeru Yanase, Yuhki Nakamura, Shun-Ichi Tsutsumi, Yasuo M. Sakai, Norio |
author_sort | Noguchi, Soma |
collection | PubMed |
description | Background and purpose: In this study, we aimed to elucidate the action mechanisms of propofol, particularly those underlying propofol-induced protein kinase C (PKC) translocation. Experimental approach: Various PKCs fused with green fluorescent protein (PKC-GFP) or other GFP-fused proteins were expressed in HeLa cells, and their propofol-induced dynamics were observed using confocal laser scanning microscopy. Propofol-induced PKC activation in cells was estimated using the C kinase activity receptor (CKAR), an indicator of intracellular PKC activation. We also examined PKC translocation using isomers and derivatives of propofol to identify the crucial structural motifs involved in this process. Key results: Propofol persistently translocated PKCα conventional PKCs and PKCδ from novel PKCs (nPKCs) to the plasma membrane (PM). Propofol translocated PKCδ and PKCη of nPKCs to the Golgi apparatus and endoplasmic reticulum, respectively. Propofol also induced the nuclear translocation of PKCζ of atypical PKCs or proteins other than PKCs, such that the protein concentration inside and outside the nucleus became uniform. CKAR analysis revealed that propofol activated PKC in the PM and Golgi apparatus. Moreover, tests using isomers and derivatives of propofol predicted that the structural motifs important for the induction of PKC and nuclear translocation are different. Conclusion and implications: Propofol induced the subtype-specific intracellular translocation of PKCs and activated PKCs. Additionally, propofol induced the nuclear translocation of PKCs and other proteins, probably by altering the permeability of the nuclear envelope. Interestingly, propofol-induced PKC and nuclear translocation may occur via different mechanisms. Our findings provide insights into the action mechanisms of propofol. |
format | Online Article Text |
id | pubmed-10662334 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106623342023-11-07 Features and mechanisms of propofol-induced protein kinase C (PKC) translocation and activation in living cells Noguchi, Soma Kajimoto, Taketoshi Kumamoto, Takuya Shingai, Masashi Narasaki, Soshi Urabe, Tomoaki Imamura, Serika Harada, Kana Hide, Izumi Tanaka, Sigeru Yanase, Yuhki Nakamura, Shun-Ichi Tsutsumi, Yasuo M. Sakai, Norio Front Pharmacol Pharmacology Background and purpose: In this study, we aimed to elucidate the action mechanisms of propofol, particularly those underlying propofol-induced protein kinase C (PKC) translocation. Experimental approach: Various PKCs fused with green fluorescent protein (PKC-GFP) or other GFP-fused proteins were expressed in HeLa cells, and their propofol-induced dynamics were observed using confocal laser scanning microscopy. Propofol-induced PKC activation in cells was estimated using the C kinase activity receptor (CKAR), an indicator of intracellular PKC activation. We also examined PKC translocation using isomers and derivatives of propofol to identify the crucial structural motifs involved in this process. Key results: Propofol persistently translocated PKCα conventional PKCs and PKCδ from novel PKCs (nPKCs) to the plasma membrane (PM). Propofol translocated PKCδ and PKCη of nPKCs to the Golgi apparatus and endoplasmic reticulum, respectively. Propofol also induced the nuclear translocation of PKCζ of atypical PKCs or proteins other than PKCs, such that the protein concentration inside and outside the nucleus became uniform. CKAR analysis revealed that propofol activated PKC in the PM and Golgi apparatus. Moreover, tests using isomers and derivatives of propofol predicted that the structural motifs important for the induction of PKC and nuclear translocation are different. Conclusion and implications: Propofol induced the subtype-specific intracellular translocation of PKCs and activated PKCs. Additionally, propofol induced the nuclear translocation of PKCs and other proteins, probably by altering the permeability of the nuclear envelope. Interestingly, propofol-induced PKC and nuclear translocation may occur via different mechanisms. Our findings provide insights into the action mechanisms of propofol. Frontiers Media S.A. 2023-11-07 /pmc/articles/PMC10662334/ /pubmed/38026993 http://dx.doi.org/10.3389/fphar.2023.1284586 Text en Copyright © 2023 Noguchi, Kajimoto, Kumamoto, Shingai, Narasaki, Urabe, Imamura, Harada, Hide, Tanaka, Yanase, Nakamura, Tsutsumi and Sakai. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Noguchi, Soma Kajimoto, Taketoshi Kumamoto, Takuya Shingai, Masashi Narasaki, Soshi Urabe, Tomoaki Imamura, Serika Harada, Kana Hide, Izumi Tanaka, Sigeru Yanase, Yuhki Nakamura, Shun-Ichi Tsutsumi, Yasuo M. Sakai, Norio Features and mechanisms of propofol-induced protein kinase C (PKC) translocation and activation in living cells |
title | Features and mechanisms of propofol-induced protein kinase C (PKC) translocation and activation in living cells |
title_full | Features and mechanisms of propofol-induced protein kinase C (PKC) translocation and activation in living cells |
title_fullStr | Features and mechanisms of propofol-induced protein kinase C (PKC) translocation and activation in living cells |
title_full_unstemmed | Features and mechanisms of propofol-induced protein kinase C (PKC) translocation and activation in living cells |
title_short | Features and mechanisms of propofol-induced protein kinase C (PKC) translocation and activation in living cells |
title_sort | features and mechanisms of propofol-induced protein kinase c (pkc) translocation and activation in living cells |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662334/ https://www.ncbi.nlm.nih.gov/pubmed/38026993 http://dx.doi.org/10.3389/fphar.2023.1284586 |
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