Sulforaphane enriched transcriptome of lung mitochondrial energy metabolism and provided pulmonary injury protection via Nrf2 in mice
Sulforaphane enriched transcriptome of lung mitochondrial energy metabolism and provided pulmonary injury protection via Nrf2 in mice
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DOI：
10.1016/j.taap.2018.12.004
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发表时间：
2019-02-01
影响因子：
3.8
通讯作者：
Kleeberger, Steven R.
中科院分区：
文献类型：
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作者：
Cho, Hye-Youn;Miller-DeGraff, Laura;Kleeberger, Steven R.
Nrf 2是抗氧化反应元件（ARE）介导的宿主防御所必需的。萝卜硫素（SFN）是一种植物化学抗氧化剂，已知在化学预防中影响多个细胞靶点，包括Nrf 2-ARE途径。然而，SFN在非恶性气道疾病中的作用仍不清楚。为了测试Nrf 2-ARE信号传导的预激活是否保护肺免受氧化剂诱导的急性损伤，在高氧或空气暴露之前，对野生型（Nrf 2（+/+））和Nrf 2缺陷型（Nrf 2（-/-））小鼠口服SFN或作为标准化西兰花芽提取物饮食（SBE）给予SFN。SFN或SBE可显著降低Nif 2（+/+）小鼠高氧诱导的肺损伤和氧化指数，但Nrf 2（-/-）小鼠无此作用。SFN仅在Nrf 2（+/+）小鼠中上调了一大簇参与线粒体氧化磷酸化、能量代谢和心血管保护的基底肺基因。生物信息学分析阐明了这些基因上的ARE样基序。在高氧暴露后，SFN处理的Nrf 2 +/+小鼠的线粒体机器基因的转录丰度仍然显著高于SFN处理的Nrf 2（-/-）小鼠。核因子-κ B被认为是受SFN影响的转录组网络中的中心分子。在Nrf 2（-/-）小鼠中，SFN对高氧引起的肺组织病理学和嗜中性粒细胞的轻微改善意味着Nrf 2独立或替代效应机制。最后，SFN
Nrf2 is essential to antioxidant response element (ARE)-mediated host defense. Sulforaphane (SFN) is a phytochemical antioxidant known to affect multiple cellular targets including Nrf2-ARE pathway in chemoprevention. However, the role of SFN in non-malignant airway disorders remain unclear. To test if pre-activation of Nrf2-ARE signaling protects lungs from oxidant-induced acute injury, wild-type (Nrf2(+/+)) and Nrf2-deficient (Nrf2(-/-)) mice were given SFN orally or as standardized broccoli sprout extract diet (SBE) before hyperoxia or air exposure. Hyperoxia-induced pulmonary injury and oxidation indices were significantly reduced by SFN or SBE in Nif2(+/+) mice but not in Nrf2(-/-) mice. SFN upregulated a large cluster of basal lung genes that are involved in mitochondrial oxidative phosphorylation, energy metabolism, and cardiovascular protection only in Nrf2(+/+) mice. Bioinformatic analysis elucidated ARE-like motifs on these genes. Transcript abundance of the mitochondrial machinery genes remained significantly higher after hyperoxia exposure in SFN-treated Nrf2+/+ mice than in SFN-treated Nrf2(-/-) mice. Nuclear factor-kappa B was suggested to be a central molecule in transcriptome networks affected by SFN. Minor improvement of hyperoxia-caused lung histopathology and neutrophilia by SFN in Nrf2(-/-) mice implies Nrf2-independent or alternate effector mechanisms. In conclusion, SFN