蛋白激酶C
激活剂(遗传学)
信号转导
缺氧诱导因子
缺氧(环境)
下调和上调
细胞生物学
生物
酶激活剂
化学
生物化学
受体
基因
氧气
有机化学
作者
Sachiko Iseki,Hiroaki Ikeda,Sayaka Kobayashi,Kazuhiro Irie,Hiroshi Harada,Hideaki Kakeya
标识
DOI:10.1021/acs.jnatprod.4c00395
摘要
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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