Induction of the nicotinamide riboside kinase NAD
Acetyl Coenzyme A
/ metabolism
Animals
Carbohydrate Dehydrogenases
/ genetics
Carnitine
/ analogs & derivatives
Female
Male
Metabolome
Mice
Mice, Inbred C57BL
Mitochondria, Muscle
/ metabolism
Muscle, Skeletal
/ metabolism
Niacinamide
/ analogs & derivatives
Phosphotransferases (Alcohol Group Acceptor)
/ genetics
Pyridinium Compounds
/ metabolism
Sarcoplasmic Reticulum
/ metabolism
Endoplasmic/sarcoplasmic reticulum
Hexose-6-phosphate dehydrogenase
Nicotinamide adenine dinucleotide
Nicotinamide riboside
Skeletal muscle
Journal
Skeletal muscle
ISSN: 2044-5040
Titre abrégé: Skelet Muscle
Pays: England
ID NLM: 101561193
Informations de publication
Date de publication:
19 02 2020
19 02 2020
Historique:
received:
08
05
2019
accepted:
15
10
2019
entrez:
21
2
2020
pubmed:
23
2
2020
medline:
29
7
2021
Statut:
epublish
Résumé
Hexose-6-Phosphate Dehydrogenase (H6PD) is a generator of NADPH in the Endoplasmic/Sarcoplasmic Reticulum (ER/SR). Interaction of H6PD with 11β-hydroxysteroid dehydrogenase type 1 provides NADPH to support oxo-reduction of inactive to active glucocorticoids, but the wider understanding of H6PD in ER/SR NAD(P)(H) homeostasis is incomplete. Lack of H6PD results in a deteriorating skeletal myopathy, altered glucose homeostasis, ER stress and activation of the unfolded protein response. Here we further assess muscle responses to H6PD deficiency to delineate pathways that may underpin myopathy and link SR redox status to muscle wide metabolic adaptation. We analysed skeletal muscle from H6PD knockout (H6PDKO), H6PD and NRK2 double knockout (DKO) and wild-type (WT) mice. H6PDKO mice were supplemented with the NAD H6PDKO skeletal muscle showed adaptations in the routes regulating nicotinamide and NAD These findings suggest a complex metabolic response to changes in muscle SR NADP(H) redox status that result in impaired mitochondrial energy metabolism and activation of cellular NAD
Sections du résumé
BACKGROUND
Hexose-6-Phosphate Dehydrogenase (H6PD) is a generator of NADPH in the Endoplasmic/Sarcoplasmic Reticulum (ER/SR). Interaction of H6PD with 11β-hydroxysteroid dehydrogenase type 1 provides NADPH to support oxo-reduction of inactive to active glucocorticoids, but the wider understanding of H6PD in ER/SR NAD(P)(H) homeostasis is incomplete. Lack of H6PD results in a deteriorating skeletal myopathy, altered glucose homeostasis, ER stress and activation of the unfolded protein response. Here we further assess muscle responses to H6PD deficiency to delineate pathways that may underpin myopathy and link SR redox status to muscle wide metabolic adaptation.
METHODS
We analysed skeletal muscle from H6PD knockout (H6PDKO), H6PD and NRK2 double knockout (DKO) and wild-type (WT) mice. H6PDKO mice were supplemented with the NAD
RESULTS
H6PDKO skeletal muscle showed adaptations in the routes regulating nicotinamide and NAD
CONCLUSIONS
These findings suggest a complex metabolic response to changes in muscle SR NADP(H) redox status that result in impaired mitochondrial energy metabolism and activation of cellular NAD
Identifiants
pubmed: 32075690
doi: 10.1186/s13395-019-0216-z
pii: 10.1186/s13395-019-0216-z
pmc: PMC7031948
doi:
Substances chimiques
Pyridinium Compounds
0
acylcarnitine
0
nicotinamide-beta-riboside
0I8H2M0L7N
Niacinamide
25X51I8RD4
Acetyl Coenzyme A
72-89-9
Carbohydrate Dehydrogenases
EC 1.1.-
galactose-6-phosphate dehydrogenase
EC 1.1.1.-
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
Nmrk2 protein, mouse
EC 2.7.1.22
Carnitine
S7UI8SM58A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/G023468/1
Pays : United Kingdom
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