Teleocidin B-4, a PKC Activator, Upregulates Hypoxia-Inducible Factor 1 (HIF-1) Activity by Promoting the Accumulation of HIF-1α Protein via the PKCα/mTORC Signaling Pathway.
J Nat Prod
; 87(6): 1666-1671, 2024 Jun 28.
Article
em En
| MEDLINE
| ID: mdl-38840407
ABSTRACT
Hypoxia-inducible factor 1 (HIF-1) signaling is upregulated in an oxygen-dependent manner under hypoxic conditions. Activation of HIF-1 signaling increases the expression of HIF-1 target genes involved in cell survival, proliferation, and angiogenesis. Therefore, compounds that activate HIF-1 signaling have therapeutic potential in ischemic diseases. Screening for compounds that activate HIF-1 activity identified a microbial metabolite, teleocidin B-4, a PKC activator. Other PKC activators, such as TPA and 10-Me-Aplog-1, also activated HIF-1 activity. PKC activators induced HIF-1α protein accumulation through PKCα/mTORC activation. These results suggest that PKC activators without tumor-promoting activity have potential as therapeutic agents via HIF-1 target gene activation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteína Quinase C-alfa
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Subunidade alfa do Fator 1 Induzível por Hipóxia
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article