AI Article Synopsis
- HIF-1 signaling is regulated by oxygen levels and is heightened in low-oxygen (hypoxic) conditions, leading to increased expression of genes that help with cell survival, growth, and the formation of new blood vessels (angiogenesis).
- Compounds that can activate HIF-1, such as the microbial metabolite teleocidin B-4 and other PKC activators, show promise for treating ischemic diseases.
- These PKC activators work by promoting the accumulation of HIF-1α protein through specific cellular pathways, indicating they could be useful therapeutic agents without the cancer-promoting effects seen in some other compounds.
Article 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.
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| http://dx.doi.org/10.1021/acs.jnatprod.4c00395 | DOI Listing |
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