Regulation of hepatic oxidative stress by voltage-gated proton channels (Hv1/VSOP) in Kupffer cells and its potential relationship with glucose metabolism.
Animals
Cell Line
Cell Line, Tumor
Glucose
/ metabolism
Hep G2 Cells
Hepatocytes
/ metabolism
Humans
Insulin Resistance
/ physiology
Ion Channels
/ metabolism
Kupffer Cells
/ metabolism
Liver
/ metabolism
Male
Mice
Mice, Inbred C57BL
Oxidative Stress
/ physiology
Protons
Reactive Oxygen Species
/ metabolism
Up-Regulation
/ physiology
Kupffer cell
blood glucose
voltage-gated proton channels
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
30
04
2020
revised:
01
09
2020
accepted:
04
09
2020
pubmed:
12
10
2020
medline:
28
4
2021
entrez:
11
10
2020
Statut:
ppublish
Résumé
Voltage-gated proton channels (Hv1/VSOP), encoded by Hvcn1, are important regulator of reactive oxygen species (ROS) production in many types of immune cells. While in vitro studies indicate that Hv1/VSOP regulates ROS production by maintaining pH homeostasis, there are few studies investigating the functional importance of Hv1/VSOP in vivo. In the present study, we first show that Hv1/VSOP is functionally expressed in liver resident macrophage, Kupffer cells, regulating the hepatic oxidative stress in vivo. Our immunocytochemistry and electrophysiology data showed that Hvcn1 is specifically expressed in Kupffer cells, but not in hepatocytes. Furthermore, Hvcn1-deficiency drastically altered the hepatic oxidative stress. The Hvcn1-deficient mice showed high blood glucose and serum insulin but normal insulin sensitivity, indicating that these phenotypes were not linked to insulin resistance. Transcriptome analysis indicated that the gene expression of glycogen phosphorylase (Pygl) and Glucose-6-phosphatase, catalytic subunit (G6pc) were upregulated in Hvcn1-deficient liver tissues, and quantitative PCR confirmed the result for Pygl. Furthermore, we observed higher amount of glucose-6-phosphate, a key sugar intermediate for glucose in Hvcn1-deficient liver than WT, suggesting that glucose production in liver is accelerated in Hvcn1-deficient mice. The present study sheds light on the functional importance of Kupffer cells in hepatic oxidative stress and its potential relationship with glucose metabolism.
Identifiants
pubmed: 33040408
doi: 10.1096/fj.202001056RRR
doi:
Substances chimiques
Hv1 proton channel, mouse
0
Ion Channels
0
Protons
0
Reactive Oxygen Species
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15805-15821Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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