Lysosome targeting fluorescent probe for NAAA imaging and its applications in the drug development for anti-inflammatory.
Int J Biol Macromol
; 263(Pt 2): 130307, 2024 Apr.
Article
de En
| MEDLINE
| ID: mdl-38382784
ABSTRACT
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Colorants fluorescents
/
Anti-inflammatoires
Langue:
En
Journal:
Int J Biol Macromol
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine