Melatonin Antagonizes Nickel-Induced Aerobic Glycolysis by Blocking ROS-Mediated HIF-1α/miR210/ISCU Axis Activation
Open Access
- 29 May 2020
- journal article
- research article
- Published by Hindawi Limited in Oxidative Medicine and Cellular Longevity
- Vol. 2020, 1-14
- https://doi.org/10.1155/2020/5406284
Abstract
Nickel and its compounds, which are well-documented carcinogens, induce the Warburg effect in normal cells by stabilizing hypoxia-inducible factor 1α (HIF-1α). 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 NiCl2, with or without 1mM 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-1α, 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-1α transcriptional activity in nickel-exposed cells. Our results indicated that ROS generation contributed to nickel-caused HIF-1α stabilization and downstream signal activation. Melatonin could antagonize HIF-1α-controlled aerobic glycolysis through ROS scavenging.Keywords
Funding Information
- Army Medical University (2019XYY01, 81872596)
This publication has 46 references indexed in Scilit:
- miR-210 Targets Iron-Sulfur Cluster Scaffold Homologue in Human Trophoblast Cell Lines: Siderosis of Interstitial Trophoblasts as a Novel Pathology of Preterm Preeclampsia and Small-for-Gestational-Age PregnanciesThe American Journal of Pathology, 2011
- Hypoxia and nickel inhibit histone demethylase JMJD1A and repress Spry2 expression in human bronchial epithelial BEAS-2B cellsCarcinogenesis: Integrative Cancer Research, 2010
- MicroRNA-210 as a Novel Therapy for Treatment of Ischemic Heart DiseaseCirculation, 2010
- Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expressionOncogene, 2010
- Melatonin protects against Nickel-induced neurotoxicity in vitro by reducing oxidative stress and maintaining mitochondrial functionJournal of Pineal Research, 2010
- MicroRNA-210 Controls Mitochondrial Metabolism during Hypoxia by Repressing the Iron-Sulfur Cluster Assembly Proteins ISCU1/2Cell Metabolism, 2009
- Regulation of Hypoxia-Inducible Factor 1α Expression and Function by the Mammalian Target of RapamycinMolecular and Cellular Biology, 2002
- Toxicity, uptake, and mutagenicity of particulate and soluble nickel compounds.Environmental Health Perspectives, 1994
- Toxicity, Uptake, and Mutagenicity of Particulate and Soluble Nickel CompoundsEnvironmental Health Perspectives, 1994
- THE METABOLISM OF TUMORS IN THE BODYThe Journal of general physiology, 1927