Allantopyrone A interferes with the degradation of hypoxia-inducible factor 1α protein by reducing proteasome activity in human fibrosarcoma HT-1080 cells.
Allantopyrone A interferes with the degradation of hypoxia-inducible factor 1α protein by reducing proteasome activity in human fibrosarcoma HT-1080 cells.
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Allantopyrone A 通过降低人纤维肉瘤 HT-1080 细胞中的蛋白酶体活性来干扰缺氧诱导因子 1α 蛋白的降解。
DOI：
10.1038/s41429-023-00610-5
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发表时间：
2023
期刊：
影响因子：
3.3
通讯作者：
Kataoka T
中科院分区：
文献类型：
--
作者：
Okuda C;Ueda Y;Muroi M;Sanada E;Osada H;Shiono Y;Kimura KI;Takeda K;Kawaguchi K;Kataoka T
Allantopyrone A是一种α-吡喃酮代谢产物，最初从内生真菌Allantophomopsis lycopodinaKS-97中分离得到。我们以前证明，allantopyrone A具有抗癌，抗炎和神经保护活性。在本研究中，我们发现，尿囊素A上调缺氧诱导因子（HIF）-1α在人纤维肉瘤HT-1080细胞中的蛋白表达。BNIP 3和ENO 1的mRNA表达上调，而其他HIF靶基因和HIF 1A的mRNA表达不上调。尿囊素A不抑制HIF-1α的脯氨酰羟基化，但增强细胞蛋白的遍在化。与此结果一致，胰凝乳蛋白酶样和胰蛋白酶样蛋白酶体活性降低，但没有完全被尿囊素A灭活。尿囊素A降低蛋白酶体催化亚基的量。因此，本研究结果表明，尿囊素A通过降低人纤维肉瘤HT-1080细胞中的蛋白酶体活性来干扰HIF-1α蛋白的降解。
Allantopyrone A is an α-pyrone metabolite that was originally isolated from the endophytic fungusAllantophomopsis lycopodinaKS-97. We previously demonstrated that allantopyrone A exhibits anti-cancer, anti-inflammatory, and neuroprotective activities. In the present study, we showed that allantopyrone A up-regulated the protein expression of hypoxia-inducible factor (HIF)-1α in human fibrosarcoma HT-1080 cells. It also up-regulated the mRNA expression ofBNIP3andENO1, but not other HIF target genes orHIF1A. Allantopyrone A did not inhibit the prolyl hydroxylation of HIF-1α, but enhanced the ubiquitination of cellular proteins. Consistent with this result, chymotrypsin-like and trypsin-like proteasome activities were reduced, but not completely inactivated by allantopyrone A. Allantopyrone A decreased the amount of proteasome catalytic subunits. Therefore, the present results showed that allantopyrone A interfered with the degradation of HIF-1α protein by reducing proteasome activity in human fibrosarcoma HT-1080 cells.