Dataset Information

N4 -Tetradentate Chelators Efficiently Regulate Copper Homeostasis and Prevent ROS Production Induced by Copper-Amyloid-?1-16.

ABSTRACT: The disruption of copper homeostasis and the oxidative stress induced by Cu-amyloids are crucial features of Alzheimer's disease pathology. The copper specific N4 -tetradendate ligands TDMQ20 and 1 are able to fully inhibit in vitro the aerobic oxidation of ascorbate induced by Cu-A?1-16 , even in the presence of 100?molar equivalents of ZnII with respect to CuII , whereas other ligands with N2 O2 or N3 O2 coordination spheres failed to do so. This essential result indicates that, in addition to metal selectivity, the coordination sphere of copper chelators should exhibit a N4 -tetradendate motif to be able to reduce an oxidative stress in the zinc-rich physiological environment of brain. The N4 -scaffolds of these two aminoquinoline-based ligands, TDMQ20 or 1, suitable for a square-planar coordination of copper(II), allowed them to enhance both the selectivity for copper and the ability to reduce the oxidative stress induced by copper-amyloid in a zinc-rich environment.

SUBMITTER: Zhang W

PROVIDER: S-EPMC6120676 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

N4 -Tetradentate Chelators Efficiently Regulate Copper Homeostasis and Prevent ROS Production Induced by Copper-Amyloid-β1-16.

Zhang Weixin W Liu Yan Y Liu Yan Y Hureau Christelle C Robert Anne A Meunier Bernard B

Chemistry (Weinheim an der Bergstrasse, Germany) 20180515 31

The disruption of copper homeostasis and the oxidative stress induced by Cu-amyloids are crucial features of Alzheimer's disease pathology. The copper specific N4 -tetradendate ligands TDMQ20 and 1 are able to fully inhibit in vitro the aerobic oxidation of ascorbate induced by Cu-Aβ1-16 , even in the presence of 100 molar equivalents of ZnII with respect to CuII , whereas other ligands with N2 O2 or N3 O2 co ...[more]

PMID: 29687932

Similar Datasets

Project description:As an essential element in plant nutrition, copper (Cu) can promote or inhibit plant growth depending on its concentration. However, the dose-dependent effects of copper, particularly on DNA damage associated with reactive oxygen species (ROS) homeostasis, are much less understood. In this work, we analyzed the dual effect of Cu (5, 20, and 60 μM) on the reproductive performance of Arabidopsis plants. Whereas Cu5 promoted inflorescence initiation and increased kilo seed weight, two higher concentrations, Cu20 and Cu60, delayed inflorescence initiation and negatively affected silique size. Excess Cu also induced changes in cellular redox homeostasis, which was examined by in situ visualization and measurements of ROS, including superoxide (O2•-), hydrogen peroxide (H2O2), malonyldialdehyde (MDA), and plasma membrane damage. The most dramatic increases in the production of O2•- and H2O2 along with increased activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX) and decreased activity of catalase (CAT) and ascorbate peroxidase (APX) were observed in roots with Cu60. Oxidative stress also modulated the expression levels of a number of genes involved in the DNA damage response (DDR), particularly those related to DNA repair. The Cu-induced chlorosis of Arabidopsis seedlings could be alleviated by exogenous addition of glutathione (GSH) and ascorbate (Asc), as the chlorophyll content was significantly increased. Overall, internal homeostasis ROS and the associated DDR pathway and the corresponding scavenging mechanisms play a central role in the response of Arabidopsis to oxidative stress induced by inhibitory Cu concentrations. Our results have shown, for the first time, that the biphasic responses of Arabidopsis seedlings to increasing Cu concentrations involve different DNA damage responses and oxidative reactions. They provide the basis for elucidating the network of Cu-induced DDR-related genes and the regulatory mechanism of the complex ROS production and scavenging system.

Project description:IntroductionThe expression of miR408 is affected by copper (Cu) conditions and positively regulates anthocyanin biosynthesis in Arabidopsis. However, the underlying mechanisms by which miR408 regulates anthocyanin biosynthesis mediated by Cu homeostasis and reactive oxygen species (ROS) homeostasis remain unclear in Malus plants.ObjectivesOur study aims to elucidate how miR408a and its target, basic blue protein (BBP) regulate Cu homeostasis and ROS homeostasis, and anthocyanin biosynthesis in Malus plants.MethodsThe roles of miR408a and its target BBP in regulating anthocyanin biosynthesis, Cu homeostasis, and ROS homeostasis were mainly identified in Malus plants.ResultsWe found that the BBP protein interacted with the copper-binding proteins LAC3 (laccase) and CSD1 (Cu/Zn SOD superoxide dismutase), indicating a potential crosstalk between Cu homeostasis and ROS homeostasis might be mediated by miR408 to regulate the anthocyanin accumulation. Further studies showed that overexpressing miR408a or suppressing BBP transiently significantly increased the expression of genes related to Cu binding and Cu transport, leading to anthocyanin accumulation under light induction in apple fruit and Malus plantlets. Consistently, opposite results were obtained when repressing miR408a or overexpressing BBP. Moreover, light induction significantly increased the expression of miR408a, CSD1, and LAC3, but significantly reduced the BBP expression, resulting in increased Cu content and anthocyanin accumulation. Furthermore, excessive Cu significantly increased the anthocyanin accumulation, accompanied by reduced expression of miR408a and Cu transport genes, and upregulated expression of Cu binding proteins including BBP, LAC3, and CSD1 to maintain the Cu homeostasis and ROS homeostasis in Malus plantlets.ConclusionOur findings provide new insights into the mechanism by which the miR408a-BBP-LAC3/CSD1 module perceives light and Cu signals regulating Cu and ROS homeostasis, ultimately affecting anthocyanin biosynthesis in Malus plants.

Dataset Information

N4 -Tetradentate Chelators Efficiently Regulate Copper Homeostasis and Prevent ROS Production Induced by Copper-Amyloid-?1-16.

Publications

N<sub>4</sub> -Tetradentate Chelators Efficiently Regulate Copper Homeostasis and Prevent ROS Production Induced by Copper-Amyloid-β<sub>1-16</sub>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets