Flavine adenine dinucleotide inhibits pathological cardiac hypertrophy and fibrosis through activating short chain acyl-CoA dehydrogenase.
Adenosine Triphosphate
/ biosynthesis
Animals
Binding Sites
Butyryl-CoA Dehydrogenase
/ genetics
Cardiomegaly
/ enzymology
Cardiotonic Agents
/ pharmacology
Cell Proliferation
/ drug effects
Energy Metabolism
/ drug effects
Enzyme Stability
Fatty Acids, Nonesterified
/ antagonists & inhibitors
Fibroblasts
/ drug effects
Fibrosis
Flavin-Adenine Dinucleotide
/ pharmacology
Gene Expression Regulation
/ drug effects
Heart Failure
/ prevention & control
Male
Molecular Dynamics Simulation
Myocardium
/ enzymology
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Multimerization
Rats
Rats, Inbred SHR
Rats, Wistar
Reactive Oxygen Species
/ antagonists & inhibitors
Cardiac fibrosis
Cardiac hypertrophy
Flavin adenine dinucleotide
Myocardial energy metabolism
Short-chain acyl-CoA dehydrogenase
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
27
03
2020
revised:
02
06
2020
accepted:
10
06
2020
pubmed:
17
6
2020
medline:
15
12
2020
entrez:
17
6
2020
Statut:
ppublish
Résumé
Short-chain acyl-CoA dehydrogenase (SCAD), the rate-limiting enzyme for fatty acid β-oxidation, has a negative regulatory effect on pathological cardiac hypertrophy and fibrosis. Furthermore, flavin adenine dinucleotide (FAD) can enhance the expression and enzyme activity of SCAD. However, whether FAD can inhibit pathological cardiac hypertrophy and fibrosis remains unclear. Therefore, we observed the effect of FAD on pathological cardiac hypertrophy and fibrosis. FAD significantly inhibited PE-induced cardiomyocyte hypertrophy and AngII-induced cardiac fibroblast proliferation. In addition, FAD ameliorated pathological cardiac hypertrophy and fibrosis in SHR. FAD significantly increased the expression and enzyme activity of SCAD. Meanwhile, ATP content was increased, the content of free fatty acids and reactive oxygen species were decreased by FAD in vivo and in vitro. In addition, molecular dynamics simulations were also used to provide insights into the structural stability and dynamic behavior of SCAD. The results demonstrated that FAD may play an important structural role on the SCAD dimer stability and maintenance of substrate catalytic pocket to increase the expression and enzyme activity of SCAD. In conclusion, FAD can inhibit pathological cardiac hypertrophy and fibrosis through activating SCAD, which may be a novel effective treatment for pathological cardiac hypertrophy and fibrosis, thus prevent them from developing into heart failure.
Identifiants
pubmed: 32540485
pii: S0006-2952(20)30336-1
doi: 10.1016/j.bcp.2020.114100
pii:
doi:
Substances chimiques
Cardiotonic Agents
0
Fatty Acids, Nonesterified
0
Reactive Oxygen Species
0
Flavin-Adenine Dinucleotide
146-14-5
Adenosine Triphosphate
8L70Q75FXE
Butyryl-CoA Dehydrogenase
EC 1.3.8.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
114100Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.