Lathyrus sativus diamine oxidase reduces Clostridium difficile toxin A-induced toxicity in Caco-2 cells by rescuing RhoA-GTPase and inhibiting pp38-MAPK/NF-κB/HIF-1α activation.
Amine Oxidase (Copper-Containing)
/ pharmacology
Bacterial Toxins
/ toxicity
Caco-2 Cells
Dietary Supplements
Enterotoxins
/ toxicity
GTP Phosphohydrolases
/ metabolism
Humans
Interleukin-6
/ metabolism
Lathyrus
/ enzymology
NF-kappa B
/ metabolism
Permeability
/ drug effects
Signal Transduction
/ drug effects
Tumor Necrosis Factor-alpha
/ metabolism
Vascular Endothelial Growth Factor A
/ metabolism
Zonula Occludens-1 Protein
/ metabolism
rhoA GTP-Binding Protein
/ metabolism
Caco-2 cells
Clostridium difficile toxin A
LSAO
RhoA-GTPase
leaky-gut
tight junctions
Journal
Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
10
04
2020
revised:
16
06
2020
accepted:
01
07
2020
pubmed:
12
9
2020
medline:
24
2
2021
entrez:
11
9
2020
Statut:
ppublish
Résumé
Clostridium difficile toxin A (TcdA) impairs the intestinal epithelial barrier, increasing the mucosa permeability and triggering a robust inflammatory response. Lathyrus sativus diamino oxidase (LSAO) is a nutraceutical compound successfully used in various gastrointestinal dysfunctions. Here, we evaluated the LSAO (0.004-0.4 μM) ability to counter TcdA-induced (30 ng/mL) toxicity and damage in Caco-2 cells, investigating its possible mechanism of action. LSAO has improved the transepithelial electrical resistance (TEER) score and increased cell viability in TcdA-treated cells, significantly rescuing the protein expression of Ras homolog family members, A-GTPase (RhoA-GTPase), occludin, and zonula occludens-1 (ZO-1). LSAO has also exhibited an anti-apoptotic effect by inhibiting the TcdA-induced expression of Bcl-2-associated X protein (Bax), p50 nuclear factor-kappa-B (p50), p65nuclear factor-kappa-B (p65), and hypoxia-inducible transcription factor-1 alpha (HIF-1α), and the release of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) in the cell milieu. Our data showed that LSAO exerts a protective effect on TcdA-induced toxicity in Caco-2 cells, placing itself as an interesting nutraceutical to supplement the current treatment of the Clostridium difficile infections.
Substances chimiques
Bacterial Toxins
0
Enterotoxins
0
IL6 protein, human
0
Interleukin-6
0
NF-kappa B
0
TJP1 protein, human
0
Tumor Necrosis Factor-alpha
0
VEGFA protein, human
0
Vascular Endothelial Growth Factor A
0
Zonula Occludens-1 Protein
0
tcdA protein, Clostridium difficile
0
RHOA protein, human
124671-05-2
Amine Oxidase (Copper-Containing)
EC 1.4.3.21
GTP Phosphohydrolases
EC 3.6.1.-
rhoA GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
415-423Subventions
Organisme : FINANZIAMENTO ANNUALE INDIVIDUALE DELLE ATTIVITA' BASE DI RICERCA, Prof. Giuseppe Esposito", LEGGE 11 DICEMBRE 2016 N.232
Organisme : Fondation Courtois (Québec, Canada)
Organisme : Joint Project Italia-Canada-Quebec (2017-2020)
Informations de copyright
© 2020 John Wiley & Sons, Ltd.
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