H-NMR and FT-IR study of the state of melatonin confined in membrane models: location and interactions of melatonin in water free lecithin and AOT reversed micelles

Bongiorno, David; Ceraulo̊, Leopoldo; Ferrugia, Mirella; Filizzola, Felice; Giordano, Cristina; Ruggirello, Angela; Liveri, Vincenzo Turco

doi:10.3998/ark.5550190.0005.522

Cited by 12 publications

(8 citation statements)

References 18 publications

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“…The molecular dynamics simulations of DOPC solutions in chloroform show that DOPC forms reverse micelles spontaneously on a 100-ns time scale (Figure S1 of the Supporting Information, SI), which is in agreement with experimental observations for similar solvents. 22 The core of reverse micelles contains polar DOPC heads, and the hydrophobic tails are exposed to chloroform (Figure S1 of the SI). We further analyzed the interaction of DOPC with graphene surface in chloroform.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Lipid Enhanced Exfoliation for Production of Graphene Nanosheets

et al. 2013

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Liquid-phase exfoliation of graphite is a widely used method to obtain graphene nanosheets, and therefore the development of a simple and efficient exfoliation procedure remains challenging. Here, we present a one-step method of graphene exfoliation in lecithin/chloroform solution. The graphene nanosheets produced by the lecithin assisted exfoliation method were analyzed by microscopy techniques, including statistical analysis of atomic force microscopy (AFM) images and Raman spectroscopy, which both indicate the presence of few-layer graphene nanosheets, including substantial content of three-layer sheets. Molecular dynamics simulations on the time scale of 0.5+ μs suggested that stability of the obtained colloid may originate from formation of lecithin reverse hemimicelles and micelles, which prevents the aggregation of exfoliated graphene flakes by entropic repulsion of the lipid hydrophobic chains.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Lipid Enhanced Exfoliation for Production of Graphene Nanosheets

et al. 2013

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“…By increasing disorder in the L d phase, melatonin displaces cholesterol, driving cholesterol into the ordered L o phase via competitive binding to lipid molecules [ 330 ]. The preferential location of melatonin at hydrophilic/hydrophobic membrane interface due to its ability to form strong H-bonds with hydrophilic lipid headgroups allows nonpolar melatonin to reverse cholesterol- and prion-induced membrane rigidity [ 762 , 789 , 790 , 791 , 792 , 793 ]. In the POPC/bovine brain sphingomyelin-supported lipid bilayer and POPC/bovine brain sphingomyelin/cholesterol-supported lipid bilayer membrane models, the PrP106–126 fragment was demonstrated to cause membrane thinning in the L o phase and membrane disintegration in the L d phase [ 329 ].…”

Section: The Effects Of Melatonin On Lipid Phase Transition Lipid Com...mentioning

confidence: 99%

Melatonin: Regulation of Prion Protein Phase Separation in Cancer Multidrug Resistance

Loh¹,

Reíter

2022

Molecules

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The unique ability to adapt and thrive in inhospitable, stressful tumor microenvironments (TME) also renders cancer cells resistant to traditional chemotherapeutic treatments and/or novel pharmaceuticals. Cancer cells exhibit extensive metabolic alterations involving hypoxia, accelerated glycolysis, oxidative stress, and increased extracellular ATP that may activate ancient, conserved prion adaptive response strategies that exacerbate multidrug resistance (MDR) by exploiting cellular stress to increase cancer metastatic potential and stemness, balance proliferation and differentiation, and amplify resistance to apoptosis. The regulation of prions in MDR is further complicated by important, putative physiological functions of ligand-binding and signal transduction. Melatonin is capable of both enhancing physiological functions and inhibiting oncogenic properties of prion proteins. Through regulation of phase separation of the prion N-terminal domain which targets and interacts with lipid rafts, melatonin may prevent conformational changes that can result in aggregation and/or conversion to pathological, infectious isoforms. As a cancer therapy adjuvant, melatonin could modulate TME oxidative stress levels and hypoxia, reverse pH gradient changes, reduce lipid peroxidation, and protect lipid raft compositions to suppress prion-mediated, non-Mendelian, heritable, but often reversible epigenetic adaptations that facilitate cancer heterogeneity, stemness, metastasis, and drug resistance. This review examines some of the mechanisms that may balance physiological and pathological effects of prions and prion-like proteins achieved through the synergistic use of melatonin to ameliorate MDR, which remains a challenge in cancer treatment.

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“…In 2005, melatonin was first observed to induce phase-separation in DPPC lipid bilayers [ 318 ]; recently, melatonin has been observed to modify lipid hydrocarbon chain order to promote phase separation in ternary membrane models [ 319 ]. Due to a preference to localize at membrane interfaces [ 320 ], melatonin can form strong hydrogen bonds with membrane lipid anionic headgroups that could significantly modulate lipid acyl chain flexibility and lipid dynamics [ 318 ]. Melatonin is able to directly interact with cholesterol [ 321 ] and displaced cholesterol due to competitive binding to lipid molecules, increasing disorder in the L d phase to drive cholesterol into the ordered L o phase [ 319 ].…”

Section: The Interdependence Between Membranes and Membraneless Organellesmentioning

confidence: 99%

“…The melatonin molecule is uncharged in the entire pH range [ 410 ] and, accordingly, in laboratory environment, the “hydrophobic” molecule is dissolved poorly in water [ 463 ] except when solubilized in pure aqueous medium by specific methodology that polarized the pyrrole ring to facilitate hydrogen bonding of the N–H group [ 464 ]. The unique ability to form strong H-bonds with hydrophilic lipid headgroups allowed nonpolar melatonin to be preferentially located at hydrophilic/hydrophobic interfaces, with complete solubility observed at the interfaces between polar and lipophilic nanodomains in reversed micelles [ 320 ]. The presence of both hydrophilic and lipophilic moieties in melatonin facilitates the scavenging of both aqueous and lipophilic free radicals [ 411 ], especially • OH [ 448 ] and • OOH, the two most prevalent ROS responsible for the chain oxidation of unsaturated phospholipids [ 465 , 466 ] in the membranes of cells and mitochondria [ 467 , 468 ].…”

Section: Melatonin Is a Potent Ancient Antioxidant That Protects Atp Levels To Regulate The Formation And Dissolution Of Mlosmentioning

confidence: 99%

Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders

Loh¹,

Reíter

2021

Antioxidants

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Biomolecular condensates are membraneless organelles (MLOs) that form dynamic, chemically distinct subcellular compartments organizing macromolecules such as proteins, RNA, and DNA in unicellular prokaryotic bacteria and complex eukaryotic cells. Separated from surrounding environments, MLOs in the nucleoplasm, cytoplasm, and mitochondria assemble by liquid–liquid phase separation (LLPS) into transient, non-static, liquid-like droplets that regulate essential molecular functions. LLPS is primarily controlled by post-translational modifications (PTMs) that fine-tune the balance between attractive and repulsive charge states and/or binding motifs of proteins. Aberrant phase separation due to dysregulated membrane lipid rafts and/or PTMs, as well as the absence of adequate hydrotropic small molecules such as ATP, or the presence of specific RNA proteins can cause pathological protein aggregation in neurodegenerative disorders. Melatonin may exert a dominant influence over phase separation in biomolecular condensates by optimizing membrane and MLO interdependent reactions through stabilizing lipid raft domains, reducing line tension, and maintaining negative membrane curvature and fluidity. As a potent antioxidant, melatonin protects cardiolipin and other membrane lipids from peroxidation cascades, supporting protein trafficking, signaling, ion channel activities, and ATPase functionality during condensate coacervation or dissolution. Melatonin may even control condensate LLPS through PTM and balance mRNA- and RNA-binding protein composition by regulating N6-methyladenosine (m6A) modifications. There is currently a lack of pharmaceuticals targeting neurodegenerative disorders via the regulation of phase separation. The potential of melatonin in the modulation of biomolecular condensate in the attenuation of aberrant condensate aggregation in neurodegenerative disorders is discussed in this review.

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H-NMR and FT-IR study of the state of melatonin confined in membrane models: location and interactions of melatonin in water free lecithin and AOT reversed micelles

Cited by 12 publications

References 18 publications

Lipid Enhanced Exfoliation for Production of Graphene Nanosheets

Lipid Enhanced Exfoliation for Production of Graphene Nanosheets

Melatonin: Regulation of Prion Protein Phase Separation in Cancer Multidrug Resistance

Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders

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