10-Hydroxydec-2-Enoic Acid Reduces Hydroxyl Free Radical-Induced Damage to Vascular Smooth Muscle Cells by Rescuing Protein and Energy Metabolism.
10-Hydroxydec-2-Enoic Acid Reduces Hydroxyl Free Radical-Induced Damage to Vascular Smooth Muscle Cells by Rescuing Protein and Energy Metabolism.
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DOI：
10.3389/fnut.2022.873892
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发表时间：
2022
影响因子：
5
通讯作者：
Li, Jianke
中科院分区：
文献类型：
--
作者：
Fan, Pei;Sha, Fangfang;Ma, Chuan;Wei, Qiaohong;Zhou, Yaqi;Shi, Jing;Fu, Jiaojiao;Zhang, Lu;Han, Bin;Li, Jianke
10-羟基-2-烯酸（10-HDA）是一种来自天然食物蜂王浆的不饱和羟基脂肪酸，具有保护细胞和组织免受损伤的作用，但其潜在机制尚不清楚。我们假设羟基自由基（•OH）的中和是10-HDA细胞保护作用的一个重要因素。在本研究中，我们发现10-HDA对•OH的清除率（2%,g/ml）大于20%，这是通过对10-HDA的-OH基团和C=C键进行多步氧化实现的。此外，10-HDA显著提高了•OH损伤血管平滑肌细胞（VSMCs）的活力（P < 0.01），显著降低了•OH诱导的细胞脂质过氧化生成丙二醛（P < 0.05），显著提高了•OH应激血管平滑肌细胞的谷胱甘肽水平（P < 0.05），表明10-HDA具有降低•OH诱导的细胞毒性的作用。对VSMCs的进一步蛋白质组学分析发现，195个蛋白在•OH刺激下表达降低，而在10-HDA拯救下表达上调，这些蛋白主要参与蛋白质合成（如翻译、蛋白质转运、核糖体和RNA结合）和能量代谢（如脂肪酸降解和糖酵解/糖异生）。综上所述，10-HDA可通过拮抗•oh诱导的VSMCs损伤而有效促进细胞存活。据我们所知，我们的结果提供了第一个具体的证据，证明10- hda清除的•OH可能是维持血管健康的潜在药理学应用。
10-Hydroxydec-2-enoic acid (10-HDA), an unsaturated hydroxyl fatty acid from the natural food royal jelly, can protect against cell and tissue damage, yet the underlying mechanisms are still unexplored. We hypothesized that the neutralization of the hydroxyl free radical (•OH), the most reactive oxygen species, is an important factor underlying the cytoprotective effect of 10-HDA. In this study, we found that the •OH scavenging rate by 10-HDA (2%, g/ml) was more than 20%, which was achieved through multiple-step oxidization of the –OH group and C=C bond of 10-HDA. Moreover, 10-HDA significantly enhanced the viability of vascular smooth muscle cells (VSMCs) damaged by •OH (P < 0.01), significantly attenuated •OH-derived malondialdehyde production that represents cellular lipid peroxidation (P < 0.05), and significantly increased the glutathione levels in •OH-stressed VSMCs (P < 0.05), indicating the role of 10-HDA in reducing •OH-induced cytotoxicity. Further proteomic analyses of VSMCs identified 195 proteins with decreased expression by •OH challenge that were upregulated by 10-HDA rescue and were primarily involved in protein synthesis (such as translation, protein transport, ribosome, and RNA binding) and energy metabolism (such as fatty acid degradation and glycolysis/gluconeogenesis). Taken together, these findings indicate that 10-HDA can effectively promote cell survival by antagonizing •OH-induced injury in VSMCs. To the best of our knowledge, our results provide the first concrete evidence that 10-HDA-scavenged •OH could be a potential pharmacological application for maintaining vascular health.
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DOI：
10.3390/molecules23102583
发表时间：
2018-10-09
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
de Carvalho CCCR;Caramujo MJ
通讯作者：
Caramujo MJ
影响因子：
1.3
作者：
Korany, Mohamed A.;Moneeb, Marwa S.;El-Banna, Alaa A.
通讯作者：
El-Banna, Alaa A.
影响因子：
10.8
作者：
Park, Seong-Cheol;Kim, Nam-Hong;Lee, Dongwon
通讯作者：
Lee, Dongwon
影响因子：
2.8
作者：
Liu, Feng;Li, Xu-Liang;Li, Lu-Sheng
通讯作者：
Li, Lu-Sheng
影响因子：
15
作者：
Sugimoto, Hideki;Kitayama, Kazuhiro;Itoh, Shinobu
通讯作者：
Itoh, Shinobu