Anthocyanins protect human endothelial cells from mild hyperoxia damage through modulation of Nrf2 pathway
Anthocyanins protect human endothelial cells from mild hyperoxia damage through modulation of Nrf2 pathway
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DOI：
10.1007/s12263-012-0324-4
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发表时间：
2013-07-01
影响因子：
3.5
通讯作者：
Saija, Antonina
中科院分区：
文献类型：
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作者：
Cimino, Francesco;Speciale, Antonio;Saija, Antonina
高氧补充的有害影响已被广泛报道。相反，人们对暴露在轻度高氧条件下的影响知之甚少，这是一个有趣的问题，因为富氧混合物的使用现在越来越多地用于临床实践，特别是出于专业和娱乐原因。我们的研究调查了人脐静脉内皮细胞(HUVECs)在体外暴露于中度高氧(O-2 32%)是否会导致细胞变化，以细胞信号通路的变化来衡量。此外，通过以人体志愿者为生物反应器的体外实验模型，我们研究了花青素代谢物是否能够保护HUVEC免受轻度高氧诱导的损伤。我们观察到，轻度高氧的细胞毒性效应伴随着转录因子Nrf2的核积累以及Nrf2调节的抗氧化剂和细胞保护基因的表达显著减少。此外，在常氧条件下，花色苷代谢产物似乎能够通过参与特定的激酶(ERK1/2)激活Nrf2途径；这种适应性效应可能解释了花色苷预处理后观察到的轻度高氧暴露的HUVEC的保护作用。本研究证实，膳食花青素和/或其代谢产物可以保护内皮细胞免受轻度高氧诱导的改变，发挥细胞信号调节剂的作用。
The detrimental effects of high oxygen supplementation have been widely reported. Conversely, few is known about the effects of exposure to mild hyperoxic conditions, an interesting issue since the use of oxygen-enriched mixture is now increasingly used in clinical practice and especially for professional and recreational reasons. Our study investigated if in vitro exposure of human umbilical vein endothelial cells (HUVECs) to moderate hyperoxia (O-2 32 %) induces cellular alterations, measured as changes in cell signaling pathways. Furthermore, by means of an ex vivo experimental model where human volunteers were used as bioreactors, we studied whether anthocyanin metabolites are able to protect HUVECs against mild hyperoxia-induced damage. We observed that the cytotoxic effect of mild hyperoxia came along with a significant decrease in nuclear accumulation of the transcription factor Nrf2, as well as in the expression of Nrf2-regulated antioxidant and cytoprotective genes. Furthermore, under normoxic conditions, anthocyanin metabolites appeared able to activate the Nrf2 pathway, through the involvement of specific kinases (ERK1/2); this adaptive effect may explain the protective effect observed in mild hyperoxia-exposed HUVECs following anthocyanin pretreatment. This study confirms that dietary anthocyanins and/or their metabolites can protect endothelial cells against mild hyperoxia-induced alterations acting as cell signaling modulators.