Sinapine targeting PLCβ3 EF hands disrupts Gαq-PLCβ3 interaction and ameliorates cardiovascular diseases
Copyright © 2023 Elsevier GmbH. All rights reserved..
BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) over-activation is highly involved in cardiovascular diseases (CVDs), with the Gαq-PLCβ3 axis acting as a core node of RAAS. PLCβ3 is a potential target of CVDs, and the lack of inhibitors has limited its drug development.
PURPOSE: Sinapine (SP) is a potential leading compound for treating CVDs. Thus, we aimed to elucidate the regulation of SP towards the Gαq-PLCβ3 axis and its molecular mechanism.
STUDY DESIGN: Aldosteronism and hypertension animal models were employed to investigate SP's inhibitory effect on the abnormal activation of the RAAS through the Gαq-PLCβ3 axis. We used chemical biology methods to identify potential targets and elucidate the underlying molecular mechanisms.
METHODS: The effects of SP on aldosteronism and hypertension were evaluated using an established animal model in our laboratory. Target identification and underlying molecular mechanism research were performed using activity-based protein profiling with a bio-orthogonal click chemistry reaction and other biochemical methods.
RESULTS: SP alleviated aldosteronism and hypertension in animal models by targeting PLCβ3. The underlying mechanism for blocking the Gαq-PLCβ3 interaction involves targeting the EF hands through the Asn-260 amino acid residue. SP regulated the Gαq-PLCβ3 axis more precisely than the Gαq-GEFT or Gαq-PKCζ axis in the cardiovascular system.
CONCLUSION: SP alleviated RAAS over-activation via Gαq-PLCβ3 interaction blockade by targeting the PLCβ3 EF hands domain, which provided a novel PLC inhibitor for treating CVDs. Unlike selective Gαq inhibitors, SP reduced the risk of side effects compared to Gαq inhibitors in treating CVDs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:126 |
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| Enthalten in: |
Phytomedicine : international journal of phytotherapy and phytopharmacology - 126(2024) vom: 29. März, Seite 155200 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chu, Simeng [VerfasserIn] |
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| Links: |
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| Themen: |
09211A0HHL |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 11.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.phymed.2023.155200 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368772616 |
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| 245 | 1 | 0 | |a Sinapine targeting PLCβ3 EF hands disrupts Gαq-PLCβ3 interaction and ameliorates cardiovascular diseases |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier GmbH. All rights reserved. | ||
| 520 | |a BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) over-activation is highly involved in cardiovascular diseases (CVDs), with the Gαq-PLCβ3 axis acting as a core node of RAAS. PLCβ3 is a potential target of CVDs, and the lack of inhibitors has limited its drug development | ||
| 520 | |a PURPOSE: Sinapine (SP) is a potential leading compound for treating CVDs. Thus, we aimed to elucidate the regulation of SP towards the Gαq-PLCβ3 axis and its molecular mechanism | ||
| 520 | |a STUDY DESIGN: Aldosteronism and hypertension animal models were employed to investigate SP's inhibitory effect on the abnormal activation of the RAAS through the Gαq-PLCβ3 axis. We used chemical biology methods to identify potential targets and elucidate the underlying molecular mechanisms | ||
| 520 | |a METHODS: The effects of SP on aldosteronism and hypertension were evaluated using an established animal model in our laboratory. Target identification and underlying molecular mechanism research were performed using activity-based protein profiling with a bio-orthogonal click chemistry reaction and other biochemical methods | ||
| 520 | |a RESULTS: SP alleviated aldosteronism and hypertension in animal models by targeting PLCβ3. The underlying mechanism for blocking the Gαq-PLCβ3 interaction involves targeting the EF hands through the Asn-260 amino acid residue. SP regulated the Gαq-PLCβ3 axis more precisely than the Gαq-GEFT or Gαq-PKCζ axis in the cardiovascular system | ||
| 520 | |a CONCLUSION: SP alleviated RAAS over-activation via Gαq-PLCβ3 interaction blockade by targeting the PLCβ3 EF hands domain, which provided a novel PLC inhibitor for treating CVDs. Unlike selective Gαq inhibitors, SP reduced the risk of side effects compared to Gαq inhibitors in treating CVDs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cardiovascular disease | |
| 650 | 4 | |a EF hands | |
| 650 | 4 | |a Gαq | |
| 650 | 4 | |a PLCs inhibitor | |
| 650 | 4 | |a Protein-protein interaction | |
| 650 | 4 | |a Sinapine | |
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| 700 | 1 | |a Shen, Fukui |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Wenjuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaoying |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Gang |e verfasserin |4 aut | |
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