Lysosome targeting fluorescent probe for NAAA imaging and its applications in the drug development for anti-inflammatory
Copyright © 2024. Published by Elsevier B.V..
N-acylethanolamine acid amidase (NAAA) is a nucleophilic lysosomal cysteine hydrolase, which primarily mediates the hydrolytic inactivation of endogenous palmitoylethanolamide (PEA), which further influences the inflammatory process by regulating peroxisome proliferator-activated receptor-α (PPAR-α). Herein, a novel lysosome (Lyso)-targeting fluorescent probe (i.e., PMBD) was designed and synthesized for detecting endogenous NAAA selectively and sensitively, allowing real-time visual monitoring of endogenous NAAA in living cells. Moreover, PMBD can target Lyso with a high colocalization in Lyso Tracker. Finally, a high-throughput assay method for NAAA inhibitor screening was established using PMBD, and the NAAA-inhibitory effects of 42 anti-inflammatory Traditional Chinese medicines were evaluated. A novel potent inhibitor of NAAA, ellagic acid, was isolated from Cornus officinalis, which can suppress LPS-induced iNOS upregulation and NO production in RAW264.7 cells that display anti-inflammatory activities. PMBD, a novel Lyso-targeting fluorescent probe for visually imaging NAAA, could serve as a useful molecular tool for exploring the physiological functions of NAAA and drug development based on NAAA-related diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:263 |
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| Enthalten in: |
International journal of biological macromolecules - 263(2024), Pt 2 vom: 26. März, Seite 130307 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Limin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.03.2024 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijbiomac.2024.130307 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2024. Published by Elsevier B.V. | ||
| 520 | |a N-acylethanolamine acid amidase (NAAA) is a nucleophilic lysosomal cysteine hydrolase, which primarily mediates the hydrolytic inactivation of endogenous palmitoylethanolamide (PEA), which further influences the inflammatory process by regulating peroxisome proliferator-activated receptor-α (PPAR-α). Herein, a novel lysosome (Lyso)-targeting fluorescent probe (i.e., PMBD) was designed and synthesized for detecting endogenous NAAA selectively and sensitively, allowing real-time visual monitoring of endogenous NAAA in living cells. Moreover, PMBD can target Lyso with a high colocalization in Lyso Tracker. Finally, a high-throughput assay method for NAAA inhibitor screening was established using PMBD, and the NAAA-inhibitory effects of 42 anti-inflammatory Traditional Chinese medicines were evaluated. A novel potent inhibitor of NAAA, ellagic acid, was isolated from Cornus officinalis, which can suppress LPS-induced iNOS upregulation and NO production in RAW264.7 cells that display anti-inflammatory activities. PMBD, a novel Lyso-targeting fluorescent probe for visually imaging NAAA, could serve as a useful molecular tool for exploring the physiological functions of NAAA and drug development based on NAAA-related diseases | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a High-throughput screening inhibitors | |
| 650 | 4 | |a Lysosome targeting | |
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| 700 | 1 | |a Tian, Manman |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Baojing |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Xudong |e verfasserin |4 aut | |
| 700 | 1 | |a Huo, Xiaokui |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Fangyu |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Xiaochi |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Xiangge |e verfasserin |4 aut | |
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