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褪黑素通过阻断 ROS 介导的 HIF-1/miR210/ISCU 轴激活来拮抗镍诱导的有氧糖酵解。

Melatonin Antagonizes Nickel-Induced Aerobic Glycolysis by Blocking ROS-Mediated HIF-1/miR210/ISCU Axis Activation.

机构信息

Department of Occupational Health, Army Medical University, 400038 Chongqing, China.

Department of Environmental Medicine, School of Public Health, and Department of Emergency Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, 310058 Hangzhou, China.

出版信息

Oxid Med Cell Longev. 2020 May 28;2020:5406284. doi: 10.1155/2020/5406284. eCollection 2020.

DOI:10.1155/2020/5406284
PMID:32566089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7275958/
Abstract

Nickel and its compounds, which are well-documented carcinogens, induce the Warburg effect in normal cells by stabilizing hypoxia-inducible factor 1 (HIF-1). Melatonin has shown diverse anticancer properties for its reactive oxygen species- (ROS-) scavenging ability. Our aim was to explore how melatonin antagonized a nickel-induced increment in aerobic glycolysis. In the current work, a normal human bronchial epithelium cell line (BEAS-2B) was exposed to a series of nonlethal doses of NiCl, with or without 1 mM melatonin. Melatonin attenuated nickel-enhanced aerobic glycolysis. The inhibition effects on aerobic glycolysis were attributed to the capability of melatonin to suppress the regulatory axis comprising HIF-1, microRNA210 (miR210), and iron-sulfur cluster assembly scaffold protein (ISCU1/2). N-Acetylcysteine (NAC) manifested similar effects as melatonin in scavenging ROS, maintaining prolyl-hydroxylase activity, and mitigating HIF-1 transcriptional activity in nickel-exposed cells. Our results indicated that ROS generation contributed to nickel-caused HIF-1 stabilization and downstream signal activation. Melatonin could antagonize HIF-1-controlled aerobic glycolysis through ROS scavenging.

摘要

镍及其化合物是有充分文献记录的致癌物质，通过稳定缺氧诱导因子 1（HIF-1）在正常细胞中诱导瓦博格效应。褪黑素因其具有清除活性氧物质（ROS）的能力而表现出多种抗癌特性。我们的目的是探讨褪黑素如何拮抗镍诱导的有氧糖酵解增加。在目前的工作中，一系列非致死剂量的 NiCl2 被暴露于正常的人支气管上皮细胞系（BEAS-2B）中，同时或不添加 1mM 褪黑素。褪黑素减弱了镍增强的有氧糖酵解。对有氧糖酵解的抑制作用归因于褪黑素抑制包含 HIF-1、miR210 和铁硫簇组装支架蛋白（ISCU1/2）的调节轴的能力。N-乙酰半胱氨酸（NAC）在清除 ROS、维持脯氨酰-羟化酶活性和减轻镍暴露细胞中 HIF-1 转录活性方面表现出与褪黑素相似的作用。我们的结果表明，ROS 的产生导致 HIF-1 的稳定和下游信号的激活。褪黑素可以通过清除 ROS 来拮抗 HIF-1 控制的有氧糖酵解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbf/7275958/58ef6b27a53c/OMCL2020-5406284.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbf/7275958/f7b44278698b/OMCL2020-5406284.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbf/7275958/58ef6b27a53c/OMCL2020-5406284.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbf/7275958/f7b44278698b/OMCL2020-5406284.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbf/7275958/6dded7d55216/OMCL2020-5406284.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbf/7275958/21175051273d/OMCL2020-5406284.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbf/7275958/419e031401a0/OMCL2020-5406284.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbf/7275958/1373baa6b458/OMCL2020-5406284.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbf/7275958/343f583c35bb/OMCL2020-5406284.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbf/7275958/8bece1eab3aa/OMCL2020-5406284.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbf/7275958/58ef6b27a53c/OMCL2020-5406284.008.jpg

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