Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, l-DOPA, and curcumin: metal binding as a general antioxidant mechanism

García, Carla R.; Angelé-Martínez, Carlos; Wilkes, Jenna A.; Wang, Hsiao-Chuan; Battin, Erin E.; Brumaghim, Julia L.

doi:10.1039/c2dt30060e

Cited by 38 publications

(32 citation statements)

References 106 publications

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“…It is reported in the literature that 0−0 as well as 0−1 bands in absorption spectra of PDI decrease simultaneously while stacking. 44 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 analysis revealed the formation of matallosupramolecular aggregates with the stoichiometric compositions (1: metal ion) of 1: 6 and 1: 2 for Fe 3+ and Cu 2+ respectively.…”

Section: Synthesis Ofmentioning

confidence: 97%

Assembly Modulation of PDI Derivative as a Supramolecular Fluorescence Switching Probe for Detection of Cationic Surfactant and Metal Ions in Aqueous Media

Dwivedi

Makam

Govindaraju

2014

ACS Appl. Mater. Interfaces

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We report an amphiphilic perylene diimide (1), a bimolecular analog of l-3,4-dihydroxyphenylalanine (L-DOPA), as a reversible fluorescence switching probe for the detection and sensing of cationic surfactants and Fe(3+)/Cu(2+) in an aqueous media respectively by means of host-guest interactions driven assembly and disassembly of 1. Photophysical studies of 1, going from dimethyl sulfoxide (DMSO) (State-I) to pure aqueous medium (State-II), suggested the formation of self-assembled aggregates by displaying very weak fluorescence emission along with red shifted broad absorption bands. Interestingly, the cationic surfactant cetyltrimethylammonium bromide (CTAB) could disassemble 1 in miceller conditions by restoring bright yellow fluorescence and vibronically well-defined (Franck-Condon progressions A0-0/A0-1 ≈ 1.6) absorption bands of 1 over other neutral and anionic surfactants (State-III). Owing to the metal chelating nature of L-DOPA, 1 was able to sense Fe(3+) and Cu(2+) among a pool of other metal ions by means of fluorescence switching off state, attributed to metal interaction driven assembly of 1 (State-IV). Such metallosupramolecular assemblies were found to reverse back to the fluorescence switching on state using a metal ion chelator, diethylenetriaminepentaacetic acid (DTPA, State-III), further signifying the role of metal ions toward assembly of 1. Formation of assembly and disassembly could be visualized by the diminished and increased yellow emission under green laser light. Further, the assembly-disassembly modulation of 1 has been extensively characterized using infrared (IR), mass spectrometry, microscopy and dynamic light scattering (DLS) techniques. Therefore, modulation of the molecular self-assembly of PDI derivative 1 in aqueous media (assembled state, State-II) by means of host-guest interactions provided by micellar structures of CTAB (disassembled state, State-III), metal ion (Fe(3+) and Cu(2+)) interactions (assembled state, State-IV) and metal ion sequestration using DTPA (disassembled state, State-III) is viewed as a supramolecular reversible fluorescence switching off-on probe for cationic surfactant CTAB and Fe(3+)/Cu(2+).

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Section: Synthesis Ofmentioning

confidence: 97%

Assembly Modulation of PDI Derivative as a Supramolecular Fluorescence Switching Probe for Detection of Cationic Surfactant and Metal Ions in Aqueous Media

Dwivedi

Makam

Govindaraju

2014

ACS Appl. Mater. Interfaces

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“…Multitude of reports have indicated the elevated concentration of labile metals in neurological disorders, generating interest to elucidate metal-neurotransmitter interactions (García et al, 2012). Halliwell and colleagues had suggested that metal ion release could be an important mechanism for the neurotoxicity of L-DOPA and related metabolites (Spencer et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

“…Further, transition metal ions have been reported to promote the toxicity of catechols, including L-DOPA (Halliwell, 2009, 1989). It has also been ascertained that the labile concentrations of copper are elevated in various malignancies (García et al, 2012). Evidence has indicated the increased redox auto oxidation of catechols in the presence of copper (Jung and Surh, 2001).…”

Section: Introductionmentioning

confidence: 99%

Copper-mediated DNA damage by the neurotransmitter dopamine and L-DOPA: A pro-oxidant mechanism

Rehmani

Zafar

Arif

et al. 2017

Toxicology in Vitro

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Oxidative DNA damage has been implicated in the pathogenesis of neurological disorders, cancer and ageing. Owing to the established link between labile copper concentrations and neurological diseases, it is critical to explore the interactions of neurotransmitters and drug supplements with copper. Herein, we investigate the pro-oxidant DNA damage induced by the interaction of L-DOPA and dopamine (DA) with copper. The DNA binding affinity order of the compounds has been determined by in silico molecular docking. Agarose gel electrophoresis reveals that L-DOPA and DA are able to induce strand scission in plasmid pcDNA3.1 (+/−) in a copper dependent reaction. These metabolites also cause cellular DNA breakage in human lymphocytes by mobilizing endogenous copper, as assessed by comet assay. Further, L-DOPA and DA-mediated DNA breaks were detected by the appearance of post-DNA damage sensitive marker γH2AX in cancer cell lines accumulating high copper. Immunofluorescence demonstrated the co-localization of downstream repair factor 53BP1 at the damaged induced γH2AX foci in cancer cells. The present study corroborates and provides a mechanism to the hypothesis that suggests metal-mediated oxidation of catecholamines contributes to the pathogenesis of neurodegenerative diseases.

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“…In this process, the antioxidant transfers hydrogen atom (HAT) or electron (ET) to neutralize the free radical [5,6], thereby preventing chain reactions such as lipid peroxidation. Other antioxidants prevent free radical formation by chelating transition metal ions such as Fe 2+ and Cu + , which are known to generate free radicals by reaction with hydrogen peroxide [7,8]. Unfortunately, many antioxidants are associated with deleterious pro-oxidant effects during which transition metal ions, such as Cu 2+ and Fe 3+ are reduced by the antioxidants to lower oxidation states (Cu + and Fe 2+ ) [9,10,11,12].…”

Section: Introductionmentioning

confidence: 99%

Effect of electron donating groups on polyphenol-based antioxidant dendrimers

et al. 2015

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Numerous studies have reported the beneficial effects of antioxidants in human diseases. Among their biological effects, a majority of antioxidants scavenge reactive radicals in the body, thereby reducing oxidative stress that is associated with the pathogenesis of many diseases. Antioxidant dendrimers are a new class of potent antioxidant compounds reported recently. In this study, six polyphenol-based antioxidant dendrimers with or without electron donating groups (methoxy group) were synthesized in order to elucidate the influence of electron donating groups (EDG) on their antioxidant activities. Syringaldehyde (2 ortho methoxy groups), vanillin (1 ortho methoxy group), and 4-hydroxybenzaldehyde (0 methoxy group) were derivatized with propargylamine to form building blocks for the dendrimers. All the six dendrimers contain polyether cores, which were synthesized by attaching pentaerythritol and methyl α-D-glucopyranoside to in-house prepared spacer units. To prepare generation 1 antioxidant dendrimers, microwave energy and granulated metallic copper catalyst were used to link the cores and building blocks together via alkyne-azide 1,3-cycloaddition click chemistry. These reaction conditions resulted in high yields of the target dendrimers that were free from copper contamination. Based on DPPH antioxidant assay, antioxidant dendrimers decorated with syringaldehyde and vanillin exhibited over 70- and 170-fold increase in antioxidant activity compared to syringaldehyde and vanillin, respectively. The antioxidant activity of dendrimers increased with increasing number of EDG groups. Similar results were obtained when the dendrimers were used to protect DNA and human LDL against organic carbon and nitrogen-based free radicals. In addition, the antioxidant dendrimers did not show any pro-oxidant activity on DNA in the presence of physiological amounts of copper. Although the dendrimers showed potent antioxidant activities against carbon and nitrogen free radicals, EPR and DNA protection studies revealed lack of effectiveness of these dendrimers against hydroxyl radicals. The dendrimers were not cytotoxic to CHO-K1 cells.

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Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, l-DOPA, and curcumin: metal binding as a general antioxidant mechanism

Cited by 38 publications

References 106 publications

Assembly Modulation of PDI Derivative as a Supramolecular Fluorescence Switching Probe for Detection of Cationic Surfactant and Metal Ions in Aqueous Media

Assembly Modulation of PDI Derivative as a Supramolecular Fluorescence Switching Probe for Detection of Cationic Surfactant and Metal Ions in Aqueous Media

Copper-mediated DNA damage by the neurotransmitter dopamine and L-DOPA: A pro-oxidant mechanism

Effect of electron donating groups on polyphenol-based antioxidant dendrimers

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