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AMPK and glucose deprivation exert an isoform-specific effect on the expression of Na$^+$,K$^+$-ATPase subunits in cultured myotubes
ID
Vidović, Anja
(
Author
),
ID
Dolinar, Klemen
(
Author
),
ID
Chibalin, Alexander V.
(
Author
),
ID
Pirkmajer, Sergej
(
Author
)
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https://link.springer.com/article/10.1007/s10974-024-09673-9
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Abstract
In skeletal muscle, Na$^+$,K$^+$-ATPase (NKA), a heterodimeric (α/β) P-type ATPase, has an essential role in maintenance of Na$^+$ and K$^+$ homeostasis, excitability, and contractility. AMP-activated protein kinase (AMPK), an energy sensor, increases the membrane abundance and activity of NKA in L6 myotubes, but its potential role in regulation of NKA content in skeletal muscle, which determines maximum capacity for Na$^+$ and K$^+$ transport, has not been clearly delineated. We examined whether energy stress and/or AMPK affect expression of NKA subunits in rat L6 and primary human myotubes. Energy stress, induced by glucose deprivation, increased protein content of NKAα1 and NKAα2 in L6 myotubes, while decreasing the content of NKAα1 in human myotubes. Pharmacological AMPK activators (AICAR, A-769662, and diflunisal) modulated expression of NKA subunits, but their effects only partially mimicked those that occurred in response to glucose deprivation, indicating that AMPK does not mediate all effects of energy stress on NKA expression. Gene silencing of AMPKα1/α2 increased protein levels of NKAα1 in L6 myotubes and NKAα1 mRNA levels in human myotubes, while decreasing NKAα2 protein levels in L6 myotubes. Collectively, our results suggest a role for energy stress and AMPK in modulation of NKA expression in skeletal muscle. However, their modulatory effects were not conserved between L6 myotubes and primary human myotubes, which suggests that coupling between energy stress, AMPK, and regulation of NKA expression in vitro depends on skeletal muscle cell model.
Language:
English
Keywords:
AMPK
,
energy stress
,
glucose
,
myotubes
,
Na$^+$
,
K$^+$-ATPase
,
skeletal muscle
Work type:
Article
Typology:
1.01 - Original Scientific Article
Organization:
MF - Faculty of Medicine
Publication status:
Published
Publication version:
Version of Record
Year:
2024
Number of pages:
Str. 139-154
Numbering:
Vol. 45, iss. 3
PID:
20.500.12556/RUL-160108
UDC:
616-092
ISSN on article:
1573-2657
DOI:
10.1007/s10974-024-09673-9
COBISS.SI-ID:
194665731
Publication date in RUL:
21.08.2024
Views:
99
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23
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Record is a part of a journal
Title:
Journal of muscle research and cell motility
Shortened title:
J. muscle res. cell motil.
Publisher:
Springer Nature
ISSN:
1573-2657
COBISS.SI-ID:
513197337
Licences
License:
CC BY 4.0, Creative Commons Attribution 4.0 International
Link:
http://creativecommons.org/licenses/by/4.0/
Description:
This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Secondary language
Language:
Slovenian
Keywords:
energijski stres
,
glukoza
,
miocevke
,
skeletna mišica
Projects
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
P3-0043
Name:
Molekularni mehanizmi razvoja in delovanja skeletne mišice
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
J7-3153
Name:
Molekularni mehanizmi specifičnosti pri uravnavanju izločanja in delovanja citokinov mišičnega izvora
Funder:
Other - Other funder or multiple funders
Funding programme:
Novo Nordisk Research Foundation
Funder:
Other - Other funder or multiple funders
Funding programme:
Karolinska Institutet, Strategic Research Programme in Diabetes
Funder:
Other - Other funder or multiple funders
Funding programme:
Russian Scientific Foundation (RNF)
Project number:
19-15-00118
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