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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Allantopyrone A activates Keap1-Nrf2 pathway and protects PC12 cells from oxidative stress-induced cell death
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Allantopyrone A activates Keap1-Nrf2 pathway and protects PC12 cells from oxidative stress-induced cell death

机译:Allantopyrone A激活Keap1-NRF2途径,保护PC12细胞免受氧化应激诱导的细胞死亡

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摘要

Keap1-Nrf2 system is known as a sensor of electrophilic compounds, and protects cells from oxidative stress through induction of various antioxidant enzymes. We found by proteomic analysis that allantopyrone A, a metabolite isolated from an endophytic fungus, upregulates the expression of proteins that are regulated by the transcription factor Nrf2. Indeed, allantopyrone A increased the antioxidant enzyme heme oxygenase-1 in PC12 cells. Moreover, it induced localization of Nrf2 in the nucleus. Affinity purification of allantopyrone A-binding protein showed that this compound could bind directly to Keap1. Allantopyrone A suppressed intracellular reactive oxygen species level and cell death induced by H2O2 in PC12 cells. These results indicate that allantopyrone A protects PC12 cells from oxidative stress-induced cell death through direct binding with Keap1 and activation of the Keap1-Nrf2 pathway.
机译:Keap1-NRF2系统被称为电子亲子化合物的传感器,并通过诱导各种抗氧化酶来保护细胞免受氧化应激。 我们发现蛋白质组学分析,即Allantopyrone A,从内生真菌中分离的代谢物,上调了转录因子NRF2调节的蛋白质的表达。 实际上,Allantopyrone A增加了PC12细胞中的抗氧化酶血红素酶-1。 此外,它诱导核中NRF2的定位。 Allantopyrone A结合蛋白的亲和纯化显示该化合物可以直接与Keap1结合。 Allantopyrone在PC12细胞中抑制了H 2 O 2诱导的细胞内反应性氧物质水平和细胞死亡。 这些结果表明,Alrantopyrone通过与Keap1直接结合和Keap1-NRF2途径的激活来保护PC12细胞免受氧化应激诱导的细胞死亡。

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