Heat Shock Cognate 70 kDa Protein Is the Target of Tetradecyl 2,3-Dihydroxybenzoate for Neuritogenic Effect in PC12 Cells.
ABPP
Alzheimer’s disease
PC12 cells
neurodegenerative disease
target identification
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
16 Oct 2021
16 Oct 2021
Historique:
received:
08
09
2021
revised:
13
10
2021
accepted:
14
10
2021
entrez:
23
10
2021
pubmed:
24
10
2021
medline:
24
10
2021
Statut:
epublish
Résumé
Tetradecyl 2,3-dihydroxybenzoate (ABG-001) is a lead compound derived from gentisides with a remarkable neuritogenic activity. However, the target of ABG-001 is yet to be defined to date. In this study, the potential target of ABG-001 was investigated via an activity-based protein profiling (ABPP) analysis, which is a chemical proteomic method for target identification by using chemical probes. Results indicated that the potential target proteins of ABG-001 were heat shock cognate 70 kDa protein (Hsc70), 78 kDa glucose-regulated protein (GRP78), and 14-3-3 theta protein. Then, the potential target of ABG-001 was confirmed by using inhibitors, the cellular thermal shift assay (CETSA) and small-interfering RNA (siRNA) analysis. The inhibitor of Hsc70 and siRNA significantly decreased the neurite outgrowth induced by ABG-001. Furthermore, ABG-001 induced neurite outgrowth was reduced by siRNA against Hsc70, and the results of CETSA suggested that Hsc70 showed a significant thermal stability-shifted effect upon ABG-001 treatment. These results indicated that Hsc70 is the target protein of ABG-001 in PC12 cells.
Identifiants
pubmed: 34680600
pii: biomedicines9101483
doi: 10.3390/biomedicines9101483
pmc: PMC8533567
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : National Natural Science Foundation of China
ID : 21877098
Organisme : the National Key R&D Program of China
ID : 2017YFE0117200
Organisme : the National Key R&D Program of China
ID : 2019YFE0100700
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