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Inhibition of the ubiquitin-proteasome system reduces the abundance of pyruvate dehydrogenase kinase 1 in cultured myotubes
ID
Kociper, Blaž
(
Avtor
),
ID
Škorja, Nives
(
Avtor
),
ID
Ogrizek, Ivana
(
Avtor
),
ID
Miš, Katarina
(
Avtor
),
ID
Pirkmajer, Sergej
(
Avtor
)
PDF - Predstavitvena datoteka,
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MD5: F8AAE35EBE6D1A4C8A8B939C88510D72
URL - Izvorni URL, za dostop obiščite
https://link.springer.com/article/10.1007/s10974-024-09679-3
Galerija slik
Izvleček
Pyruvate dehydrogenase kinase (PDK), which phosphorylates the pyruvate dehydrogenase complex, regulates glucose metabolism in skeletal muscle. PDK1, an isozyme whose expression is controlled by hypoxia-inducible factor-1α (HIF-1α), is thought to play a role in muscle adaptation to hypoxia. While transcriptional upregulation of PDK1 by HIF-1α is well characterised, mechanisms controlling proteolysis of PDK1 in skeletal muscle have not been thoroughly investigated. Proteasome inhibitor MG132 paradoxically reduced the abundance of PDK1 in human cancer cells and rat L6 myotubes, suggesting that MG132 might direct PDK1 towards autophagic degradation. The objectives of our current study were to determine (1) whether MG132 suppresses PDK1 levels in primary human myotubes, (2) whether chloroquine, an inhibitor of autophagy, prevents MG132-induced suppression of PDK1 in L6 myotubes, and (3) whether PYR-41, an inhibitor of ubiquitination, suppresses PDK1 in L6 myotubes. Using qPCR and/or immunoblotting, we found that despite markedly upregulating HIF-1α protein, MG132 did not alter the PDK1 expression in cultured primary human myotubes, while it suppressed both PDK1 mRNA and protein in L6 myotubes. The PDK1 levels in L6 myotubes were suppressed also during co-treatment with chloroquine and MG132. PYR-41 markedly increased the abundance of HIF-1α in primary human and L6 myotubes, while reducing the abundance of PDK1. In L6 myotubes treated with PYR-41, chloroquine increased the abundance of the epidermal growth factor receptor, but did not prevent the suppression of PDK1. Collectively, our results suggest that cultured myotubes degrade PDK1 via a pathway that cannot be inhibited by MG132, PYR-41, and/or chloroquine.
Jezik:
Angleški jezik
Ključne besede:
chloroquine
,
hypoxia-inducible factor-1α
,
HIF-1α
,
MG132
,
myotubes
,
PYR-41
,
pyruvate dehydrogenase kinase 1
,
PDK1
Vrsta gradiva:
Članek v reviji
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
MF - Medicinska fakulteta
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2024
Št. strani:
Str. 155–169
Številčenje:
Vol. 45, iss. 3
PID:
20.500.12556/RUL-160122
UDK:
616-092
ISSN pri članku:
1573-2657
DOI:
10.1007/s10974-024-09679-3
COBISS.SI-ID:
203573251
Datum objave v RUL:
21.08.2024
Število ogledov:
48
Število prenosov:
4
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Objavi na:
Gradivo je del revije
Naslov:
Journal of muscle research and cell motility
Skrajšan naslov:
J. muscle res. cell motil.
Založnik:
Springer Nature
ISSN:
1573-2657
COBISS.SI-ID:
513197337
Licence
Licenca:
CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:
http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:
To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
klorokin
,
hipoksijsko inducibilni faktor-1α
,
HIF-1α
,
miocevke
,
piruvat dehidrogenaza kinaza 1
,
PDK1
Projekti
Financer:
ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:
P3-0043
Naslov:
Molekularni mehanizmi razvoja in delovanja skeletne mišice
Financer:
ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:
J7-3153
Naslov:
Molekularni mehanizmi specifičnosti pri uravnavanju izločanja in delovanja citokinov mišičnega izvora
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