Chelating and antioxidant properties of l-Dopa containing tetrapeptide for the treatment of neurodegenerative diseases

Cacciatore, Ivana; Marinelli, Lisa; Stefano, Antonio Di; Marco, Valerio Di; Orlando, Giustino; Gabriele, Mirko; Gatta, Daniela Maria Pia; Ferrone, Alessio; Franceschelli, Sara; Speranza, Lorenza; Patruno, Antonia

doi:10.1016/j.npep.2018.06.002

Cited by 11 publications

(13 citation statements)

References 43 publications

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“…Superoxide dismutase (SOD, EC 1.15.1.1) activity was performed as previously described [19] using an assay mixture containing sodium carbonate buffer (50 mM, pH 10) epinephrine (0.1 mM), and fresh cell lysate (containing 25 μg of protein) in a final volume of 200 μL [20]. Percentage inhibition values were converted into activities by using a purified Cu, Zn bovine SOD as standard.…”

Section: Methodsmentioning

confidence: 99%

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Modulation of Apoptotic Cell Death and Neuroprotective Effects of Glutathione—L-Dopa Codrug Against H2O2-Induced Cellular Toxicity

et al. 2019

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The L-3,4-dihydroxyphenylalanine (LD) is the gold standard drug currently used to manage Parkinson’s disease (PD) and to control its symptoms. However, LD could cause disease neurotoxicity due to the generation of pro-oxidant intermediates deriving from its autoxidation. In order to overcome this limitation, we have conjugated LD to the natural antioxidant glutathione (GSH) to form a codrug (GSH-LD). Here we investigated the effect of GSH-LD on H2O2-induced cellular toxicity in undifferentiated and differentiated lymphoma U-937 and dopaminergic neuroblastoma SH-SY5Y cell lines, used respectively as models to study the involvement of macrophages/microglia and dopaminergic neurons in PD. We analyzed the effect of GSH-LD on apoptosis and cellular oxidative stress, both considered strategic targets for the prevention and treatment of neurodegenerative diseases. Compared to LD and GSH, GSH-LD had a stronger effect in preventing hydrogen peroxide (H2O2) induced apoptosis in both cell lines. Moreover, GSH-LD was able to preserve cell viability, cellular redox status, gluthation metabolism and prevent reactive oxygen species (ROS) formation, in a phosphinositide 3-kinase (PI3K)/kinase B (Akt)-dependent manner, in a neurotoxicity cellular model. Our findings indicate that the GSH-LD codrug offers advantages deriving from the additive effect of LD and GSH and it could represent a promising candidate for PD treatment.

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Section: Methodsmentioning

confidence: 99%

“…Catalase (CAT, EC 1.11.1.6), glutathione peroxidase (GPx, EC 1.11.1.9) and glutathione reductase (GR, EC 1.8.1.7) activity was measured as described previously [20]. CAT activity was measured spectrophotometrically monitoring the decomposition of H 2 O 2 at 240 nm.…”

Section: Methodsmentioning

confidence: 99%

Modulation of Apoptotic Cell Death and Neuroprotective Effects of Glutathione—L-Dopa Codrug Against H2O2-Induced Cellular Toxicity

et al. 2019

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“…Ellagic acid [214] Entacapone (Comtan, ASI-6) [12,215,216] Enzastaurin [164] Epicatechin [128,160,193,194] Epigallocatechin-3-gallate [117,217,218] Etidronate (HEDPA) [219] Exifone [12] F13714 [220] F15599 [220,221] Farrerol [222] Fisetin (3,3 ,4 ,7-Tetrahydroxy flavone) [223][224][225] Fraxetin [117] Galangin [226] Gallic acid and derivatives [214,227,228] Gallocatechin [128] Garcinol [229] Genistein [117,128,230,231] Glutamine [232] Glutathione derivatives [63] Glutathione -hydroxyquinoline compound [233] Glutathione-l-DOPA compound [234] Gly-N-C-DOPA [209] GSK2795039 [108] Guanabenz [235] Hesperidin [128,236] Hinokitiol […”

Section: Compound Name(s) Referencesmentioning

confidence: 99%

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

Tosato

Marco

2019

Biomolecules

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The present review reports a list of approximately 800 compounds which have been used, tested or proposed for Parkinson’s disease (PD) therapy in the year range 2014–2019 (April): name(s), chemical structure and references are given. Among these compounds, approximately 250 have possible or established metal-chelating properties towards Cu(II), Cu(I), Fe(III), Fe(II), Mn(II), and Zn(II), which are considered to be involved in metal dyshomeostasis during PD. Speciation information regarding the complexes formed by these ions and the 250 compounds has been collected or, if not experimentally available, has been estimated from similar molecules. Stoichiometries and stability constants of the complexes have been reported; values of the cologarithm of the concentration of free metal ion at equilibrium (pM), and of the dissociation constant Kd (both computed at pH = 7.4 and at total metal and ligand concentrations of 10–6 and 10–5 mol/L, respectively), charge and stoichiometry of the most abundant metal–ligand complexes existing at physiological conditions, have been obtained. A rigorous definition of the reported amounts is given, the possible usefulness of this data is described, and the need to characterize the metal–ligand speciation of PD drugs is underlined.

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“…ROS measurement was performed as described previously [28]. Cells (5 × 10 5 ) were resuspended with carboxy-2 ,7 -dichloro-dihydro-fluorescein diacetate (DCFH-DA Sigma, St Louis, MO, USA) probe and incubated at 37 • C for 30 min in the dark.…”

Section: Ros Production Analysismentioning

confidence: 99%

Anti-Migratory Effects of 4′-Geranyloxyferulic Acid on LPS-Stimulated U937 and HCT116 Cells via MMP-9 Down-Regulation: Involvement of ROS/ERK Signaling Pathway

et al. 2020

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Matrix metalloproteinases (MMPs) play a crucial role in tumor angiogenesis, and metastasis. 4′-geranyloxyferulic acid (GOFA) has anti-tumor and anti-inflammatory proprieties. Herein, we aimed to determine whether this compound affects cell survival, invasion, and migration through reactive oxygen species (ROS)-mediated MMPs activation of extracellular signal-regulated kinases (ERKs) and p38 signaling in lymphocytic histiocytoma (U937) and colorectal cancer (HCT116) cells. We observed that lipopolysaccharide (LPS) stimulated U937 and HCT116 cells presented abnormal cell proliferation and increased metalloproteinase (MMP-9) activity and expression. Non-cytotoxic doses of GOFA blunted matrix invasive potential by reducing LPS-induced MMP-9 expression and cell migration via inhibiting ROS/ ERK pathway. GOFA also attenuated apoptosis and cell senescence. Our findings indicate that GOFA, inhibiting cancer cell proliferation and migration, could be therapeutically beneficial to prevent tumor metastasis.

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Chelating and antioxidant properties of l-Dopa containing tetrapeptide for the treatment of neurodegenerative diseases

Cited by 11 publications

References 43 publications

Modulation of Apoptotic Cell Death and Neuroprotective Effects of Glutathione—L-Dopa Codrug Against H2O2-Induced Cellular Toxicity

Modulation of Apoptotic Cell Death and Neuroprotective Effects of Glutathione—L-Dopa Codrug Against H2O2-Induced Cellular Toxicity

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

Anti-Migratory Effects of 4′-Geranyloxyferulic Acid on LPS-Stimulated U937 and HCT116 Cells via MMP-9 Down-Regulation: Involvement of ROS/ERK Signaling Pathway

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