Thiamine and benfotiamine protect neuroblastoma cells against paraquat and β-amyloid toxicity by a coenzyme-independent mechanism.
ARE, antioxidant response element
BFT, benfotiamine
Cell biology
FBS, fetal bovine serum
Neuroscience
O-BT, O-benzoylthiamine
PQ, paraquat
ROS, reactive oxygen species
S-BT, S-benzoylthiamine
SuBT, sulbutiamine
TPK, thiamine pyrophosphokinase
ThDP, thiamine diphosphate
ThMP, thiamine monophosphate
Journal
Heliyon
ISSN: 2405-8440
Titre abrégé: Heliyon
Pays: England
ID NLM: 101672560
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
24
09
2018
revised:
21
02
2019
accepted:
08
05
2019
entrez:
14
6
2019
pubmed:
14
6
2019
medline:
14
6
2019
Statut:
epublish
Résumé
Benfotiamine (BFT) is a synthetic thiamine precursor with high bioavailability. It is efficient in treating complications of type 2 diabetes and has beneficial effects in mouse models of neurodegenerative diseases. The mechanism of action of BFT remains unknown, though it is sometimes suggested that it may be linked to increased thiamine diphosphate (ThDP) coenzyme function. We used a mouse neuroblastoma cell line (Neuro2a) grown in thiamine-restricted medium. The cells were stressed by exposure to paraquat (PQ) or amyloid β At 50 μM, BFT protects the cells against PQ and amyloid β BFT, SuBT and thiamine all protect the cells against oxidative stress, suggesting an antioxidant effect of thiamine. Our results are not in favor of a direct ROS scavenging effect of thiamine but rather an indirect effect possibly mediated by some antioxidant signaling pathway. It is however not clear whether this effect is due to thiamine itself, its thiol form or an unknown metabolite. Our results suggest a role of thiamine in protection against oxidative stress, independent of the coenzyme function of thiamine diphosphate.
Sections du résumé
BACKGROUND
BACKGROUND
Benfotiamine (BFT) is a synthetic thiamine precursor with high bioavailability. It is efficient in treating complications of type 2 diabetes and has beneficial effects in mouse models of neurodegenerative diseases. The mechanism of action of BFT remains unknown, though it is sometimes suggested that it may be linked to increased thiamine diphosphate (ThDP) coenzyme function.
METHODS
METHODS
We used a mouse neuroblastoma cell line (Neuro2a) grown in thiamine-restricted medium. The cells were stressed by exposure to paraquat (PQ) or amyloid β
RESULTS
RESULTS
At 50 μM, BFT protects the cells against PQ and amyloid β
CONCLUSIONS
CONCLUSIONS
BFT, SuBT and thiamine all protect the cells against oxidative stress, suggesting an antioxidant effect of thiamine. Our results are not in favor of a direct ROS scavenging effect of thiamine but rather an indirect effect possibly mediated by some antioxidant signaling pathway. It is however not clear whether this effect is due to thiamine itself, its thiol form or an unknown metabolite.
GENERAL SIGNIFICANCE
CONCLUSIONS
Our results suggest a role of thiamine in protection against oxidative stress, independent of the coenzyme function of thiamine diphosphate.
Identifiants
pubmed: 31193162
doi: 10.1016/j.heliyon.2019.e01710
pii: S2405-8440(18)35887-0
pii: e01710
pmc: PMC6520661
doi:
Types de publication
Journal Article
Langues
eng
Pagination
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