Multi-site binding of epigallocatechin gallate to human serum albumin measured by NMR and isothermal titration calorimetry

Eaton, Joshua D.; Williamson, Mike

doi:10.1042/bsr20170209

Cited by 21 publications

(16 citation statements)

References 37 publications

(56 reference statements)

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“…EGCG reaches maximum plasma concentration 2 h after drinking a cup of green tea, but the steady-state concentration may be much higher for frequent green tea drinkers ( 70 ). Studies with human serum albumin (HSA) indicate that EGCG binds to two high-affinity sites ( K D = 22 μ m ) and several additional low-affinity surface sites (m m K D ), suggesting that plasma concentrations of HSA (∼600 μ m ) can bind up to 98% of EGCG ( 71 ). This would account for the slow metabolism of EGCG but could also restrict its availability for interactions with amyloid proteins, including Aβ, α-synuclein, and apoA-I.…”

Section: Discussionmentioning

confidence: 99%

“…This would account for the slow metabolism of EGCG but could also restrict its availability for interactions with amyloid proteins, including Aβ, α-synuclein, and apoA-I. However, as Eaton and Williamson point out in their recent work ( 71 ), the weaker (millimolar) binding implies fast off-rates and the weakly bound EGCG would dissociate at a rate of 100 s −1 or faster (assuming the association rate is at the diffusion-limit). Hence, the exchange of EGCG between HSA and tissue is likely to be rapid.…”

Section: Discussionmentioning

confidence: 99%

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Epigallocatechin-3-gallate remodels apolipoprotein A-I amyloid fibrils into soluble oligomers in the presence of heparin

Townsend

Hughes

Akien

et al. 2018

Journal of Biological Chemistry

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Amyloid deposits of WT apolipoprotein A-I (apoA-I), the main protein component of high-density lipoprotein, accumulate in atherosclerotic plaques where they may contribute to coronary artery disease by increasing plaque burden and instability. Using CD analysis, solid-state NMR spectroscopy, and transmission EM, we report here a surprising cooperative effect of heparin and the green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG), a known inhibitor and modulator of amyloid formation, on apoA-I fibrils. We found that heparin, a proxy for glycosaminoglycan (GAG) polysaccharides that co-localize ubiquitously with amyloid in vivo, accelerates the rate of apoA-I formation from monomeric protein and associates with insoluble fibrils. Mature, insoluble apoA-I fibrils bound EGCG (KD = 30 ± 3 μm; Bmax = 40 ± 3 μm), but EGCG did not alter the kinetics of apoA-I amyloid assembly from monomer in the presence or absence of heparin. EGCG selectively increased the mobility of specific backbone and side-chain sites of apoA-I fibrils formed in the absence of heparin, but the fibrils largely retained their original morphology and remained insoluble. By contrast, fibrils formed in the presence of heparin were mobilized extensively by the addition of equimolar EGCG, and the fibrils were remodeled into soluble 20-nm-diameter oligomers with a largely α-helical structure that were nontoxic to human umbilical artery endothelial cells. These results argue for a protective effect of EGCG on apoA-I amyloid associated with atherosclerosis and suggest that EGCG-induced remodeling of amyloid may be tightly regulated by GAGs and other amyloid co-factors in vivo, depending on EGCG bioavailability.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-gallate remodels apolipoprotein A-I amyloid fibrils into soluble oligomers in the presence of heparin

Townsend

Hughes

Akien

et al. 2018

Journal of Biological Chemistry

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“…Similar nature of interaction has been reported for HSA-EGCG interaction where two separate binding events occur. There is initial strong binding between HSA and EGCG followed by 1,000 times weaker secondary binding event 34 . EGCG is thought to act via a common mechanism for various aggregation prone proteins.…”

Section: Egcg Interacts With Tau In a Multiple Binding Eventmentioning

confidence: 99%

EGCG impedes human Tau aggregation and interacts with Tau

Sonawane

Chidambaram

Boral

et al. 2020

Sci Rep

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Tau aggregation and accumulation is a key event in the pathogenesis of Alzheimer's disease. Inhibition of Tau aggregation is therefore a potential therapeutic strategy to ameliorate the disease. Phytochemicals are being highlighted as potential aggregation inhibitors. Epigallocatechin-3-gallate (EGCG) is an active phytochemical of green tea that has shown its potency against various diseases including aggregation inhibition of repeat Tau. The potency of EGCG in altering the PHF assembly of full-length human Tau has not been fully explored. By various biophysical and biochemical analyses like ThS fluorescence assay, MALDI-TOF analysis and Isothermal Titration Calorimetry, we demonstrate dual effect of EGCG on aggregation inhibition and disassembly of full-length Tau and their binding affinity. The IC50 for Tau aggregation by EGCG was found to be 64.2 μM. Abbreviations EGCG Epigallocatechin-3-gallate AD Alzheimer's disease Aβ Amyloid-β IAPP Islet amyloid polypeptide ITC Isothermal titration calorimetry TEM Transmission electron microscopy SEC Size exclusion chromatography MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ThS Thioflavin S ANS 8-Anilino-1-naphthalenesulfonic acid ammonium salt The direct causal relationship between neurodegenerative disorders and protein misfolding has been debatable over years 1-3. The recent advances in studies of misfolded proteins to some extent have shed the light upon the cause-effect interdependence of proteins and diseases 4. Neurodegenerative diseases are diverse in nature at physiological as well as molecular level. For example, the misfolded proteins involved in Alzheimer's disease (AD) are amyloid-β (Aβ) and Tau (Fig. 1A) whereas 5 ; α-Synuclein is a key player in Parkinson's disease. AD is phenotypically characterized by gradual memory loss due to neuronal death 6. The molecular pathology involves abnormal accumulation of Aβ plaques 7 in the extracellular milieu and cytoplasmic Tau tangles 8,9. Tau aggregation increases load on clearance machinery of neurons, which finally collapses, and results in neuronal death 10,11. The physiological function of Tau is to bind microtubules and stabilize them thus aiding in neuronal functioning 12,13. Tau aggregates abnormally due to multiple factors-like mutations, aberrant post-translational modifications, oxidative stress etc. 14-16. Abnormal phosphorylation of Tau is one of the key factors implied in its aggregation 17,18. The factors leading to Tau aggregation have directed the researchers to design and develop the therapeutics against Tau aggregation and AD. Several classes of compounds showing potency in inhibiting Tau aggregation include phenothiazines 19,20 , anthraquinones 21 , porphyrins, aminothienopyridazines 22 , natural compounds (polyphenols 23 , secondary metabolites 24 , curcumin 25 , Oleocanthal 26 etc.). The phenothiazine compounds inhibit Tau-Tau (repeat domain) binding thus preventing Tau aggregation. These compounds have

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“…An unexpected high amount of bound EGCG was found when the affinity of EGCG for human serum albumin was tested in physiological conditions. These results imply that almost all EGCG is transported in the blood bound to albumin, and explains the wide tissue distribution and chemical stability of EGCG in vivo [14]. EGCG kinetics have also been studied in rat and mouse models.…”

Section: Structure Bioavailability and Metabolism Of Epigallocatementioning

confidence: 99%

Epigallocatechin Gallate Modulates Muscle Homeostasis in Type 2 Diabetes and Obesity by Targeting Energetic and Redox Pathways: A Narrative Review

Casanova

Salvadó

Crescenti

et al. 2019

IJMS

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Obesity is associated with the hypertrophy and hyperplasia of adipose tissue, affecting the healthy secretion profile of pro- and anti-inflammatory adipokines. Increased influx of fatty acids and inflammatory adipokines from adipose tissue can induce muscle oxidative stress and inflammation and negatively regulate myocyte metabolism. Muscle has emerged as an important mediator of homeostatic control through the consumption of energy substrates, as well as governing systemic signaling networks. In muscle, obesity is related to decreased glucose uptake, deregulation of lipid metabolism, and mitochondrial dysfunction. This review focuses on the effect of epigallocatechin-gallate (EGCG) on oxidative stress and inflammation, linked to the metabolic dysfunction of skeletal muscle in obesity and their underlying mechanisms. EGCG works by increasing the expression of antioxidant enzymes, by reversing the increase of reactive oxygen species (ROS) production in skeletal muscle and regulating mitochondria-involved autophagy. Moreover, EGCG increases muscle lipid oxidation and stimulates glucose uptake in insulin-resistant skeletal muscle. EGCG acts by modulating cell signaling including the NF-κB, AMP-activated protein kinase (AMPK), and mitogen-activated protein kinase (MAPK) signaling pathways, and through epigenetic mechanisms such as DNA methylation and histone acetylation.

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Multi-site binding of epigallocatechin gallate to human serum albumin measured by NMR and isothermal titration calorimetry

Cited by 21 publications

References 37 publications

Epigallocatechin-3-gallate remodels apolipoprotein A-I amyloid fibrils into soluble oligomers in the presence of heparin

Epigallocatechin-3-gallate remodels apolipoprotein A-I amyloid fibrils into soluble oligomers in the presence of heparin

EGCG impedes human Tau aggregation and interacts with Tau

Epigallocatechin Gallate Modulates Muscle Homeostasis in Type 2 Diabetes and Obesity by Targeting Energetic and Redox Pathways: A Narrative Review

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