This force field has been shown to be highly accurate in describing both local and long-range structural properties of p53 NTD This resulted in an effective concentration of 2. Energy minimization using the steepest descent algorithm was first conducted to remove potential steric clashes in the initial conformation. Mean volume of the system was calculated for this simulation, and the conformation whose volume was closest to the mean volume was selected as the starting conformation for later REST2 simulations.
In all simulations, short-range nonbonded interactions were truncated at 1. The particle mesh Ewald PME method 66 was used to treat long-range electrostatic interactions.
NTD construct 20—70 was purified as described above. The monodispersity of protein was confirmed by a single peak in DLS, as shown in the Supplementary Fig. Prior to data collection, samples were thawed, filtered pore size 0. Quartz capillary with a path length of 1. Most samples showed no detectable radiation damage, which was monitored by averaging 20 frames.
To obtain scattering intensity profiles, 20 data frames were reduced to scattering intensity profiles, placed on an absolute scale, averaged, and the scattering intensity profile of the buffer match was subtracted. The resulting models were aligned, grouped into clusters, averaged, and the average model was refined in Dammiff 77 , 78 , For Fig. The samples were scanned with the time interval between scans set to zero.
First, SPR was used to study the kinetics and binding affinity of the interaction between MDM2 and full-length p53 as described before. With the increase of concentration of EGCG in the solution, the binding signal to the chip will decrease. Fluorescence anisotropy measurements were made in opaque, round-bottom well polystyrene plates using a Molecular Devices i3x plate reader with the Fluorescein-FP cartridge. Full-length p53 was desalted into the same buffer, and two-fold serial-dilutions were prepared in the well plate.
Experimental measurements of parallel and perpendicular fluorescence were blank subtracted using a pair of matched dilution series prepared without fluor—MDM2 to correct for background fluorescence, then converted to anisotropy.
The results were plotted versus p53 concentration and fit to a one-site binding equation. K D and standard error values were determined by inverse-variance weighted pooling of the fit parameters from two replicates.
Lyophilized ubiquitin was directly resuspended in the same buffer. The gels were imaged on an Azure Biosystems Sapphire biomolecular imager. The fluorescein channel was exported, and the extent of ubiquitination was quantified in BioRad ImageLab 6.
Further information on research design is available in the Nature Research Reporting Summary linked to this article.
Data supporting the findings of this manuscript are available from the corresponding author upon reasonable request. A reporting summary for this Article is available as a Supplementary Information file. Source data are provided with this paper. Du, G. Epigallocatechin gallate EGCG is the most effective cancer chemopreventive polyphenol in green tea. Nutrients 4 , — Khan, N. Targeting multiple signaling pathways by green tea polyphenol - -epigallocatechingallate.
Cancer Res. Lee, M. Analysis of plasma and urinary tea polyphenols in human subjects. Cancer Epidemiol. CAS Google Scholar. Lambert, J.
Cancer chemopreventive activity and bioavailability of tea and tea polyphenols. Gan, R. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate EGCG : an updated review. Food Sci. Google Scholar. Imai, K. Cancer-preventive effects of drinking green tea among a Japanese population. Nakachi, K. Preventive effects of drinking green tea on cancer and cardiovascular disease: epidemiological evidence for multiple targeting prevention.
Biofactors 13 , 49—54 Shin, C. Green tea extracts for the prevention of metachronous colorectal polyps among patients who underwent endoscopic removal of colorectal adenomas: a randomized clinical trial. Gupta, S. Molecular pathway for - -epigallocatechingallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells. Chung, L. Induction of apoptosis by green tea catechins in human prostate cancer DU cells.
Life Sci. Lee, J. EGCG induces apoptosis in human laryngeal epidermoid carcinoma Hep2 cells via mitochondria with the release of apoptosis-inducing factor and endonuclease G. Cancer Lett. Qin, J. Cerezo-Guisado, M. Food Chem. Fassina, G. Mechanisms of inhibition of tumor angiogenesis and vascular tumor growth by epigallocatechingallate. Luo, K. Ermakova, S. Shim, J.
Epigallocatechin gallate suppresses lung cancer cell growth through Ras—GTPase-activating protein SH3 domain-binding protein 1. Cancer Prev Res. Yamauchi, R. Identification of epigallocatechingallate in green tea polyphenols as a potent inducer of pdependent apoptosis in the human lung cancer cell line A In Vitro 23 , — Thakur, V.
Bode, A. Post-translational modification of p53 in tumorigenesis. Cancer 4 , — Labuschagne, C. Control of metabolism by p53—cancer and beyond. Acta 56 , — Mihara, M. P53 has a direct apoptogenic role at the mitochondria. Cell 11 , — Zhang, Q. Making it a sensible option for oral drug delivery.
The multi-etiological character of neurodegenerative diseases demands the need for the development of therapeutic agents capable of manipulating multiple desired targets. Green tea polyphenols, in particular EGCG is able to fulfil this criterion both in vitro and in vivo. These properties together give EGCG its neuroprotective and neurorescue abilities.
Therefore, with the support from this data we propose EGCG as an iron chelating - brain permeable - antioxidant agent, which can modulate multiple brain targets. However, there is a need for examining this neuroprotective effect in depth through human clinical trials, since presently very few studies have delved into this subject.
PMID: Molecular pathways to neurodegeneration. Nat Med. Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Sheridan C. Nat Biotechnol. Free Radic Biol Med. J Nutr Biochem.
Green tea polyphenol epigallocatechingallate: inflammation and arthritis. Life Sci. Elsevier Inc. Health benefits of tea consumption. Trop J Pharm Res. Article Google Scholar. The antioxidant and pro-oxidant activities of green tea polyphenols: A role in cancer prevention.
Arch Biochem Biophys. Distinct effects of tea catechins on 6-hydroxydopamine-induced apoptosis in PC12 cells. Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence SAMP Exp Gerontol.
Daily consumption of green tea catechin delays memory regression in aged mice. Mol Neurobiol. J Biol Chem. Multifunctional activities of green tea catechins in neuroprotection. Green tea polyphenol - -epigallocatechingallate promotes the rapid protein kinase C- and proteasome-mediated degradation of Bad: Implications for neuroprotection.
J Neurochem. Total phenol, catechin, and caffeine contents of teas commonly consumed in the United Kingdom. J Agric Food Chem. Scavenging effects of tea catechins and their derivatives on 1,1- diphenylpicrylhydrazyl radical. Targeting multiple signaling pathways by green tea polyphenol - -epigallocatechingallate.
Cancer Res. J Neurol Neurosurg Psychiatry. Ritchie K, Lovestone S. The dementias. Green tea consumption and cognitive function: A cross-sectional study from the Tsurugaya Project.
Am J Clin Nutr. Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. Adv Nutr. Am J Epidemiol.
PubMed Article Google Scholar. Mov Disord. Habitual intake of dietary flavonoids and risk of Parkinson disease. J Am Coll Nutr. J Neurol Sci. Analysis of plasma and urinary tea polyphenols in human subjects. Cancer EpidemiolBiomarkers Prev. CAS Google Scholar. Dose-dependent incorporation of tea catechins, - -epigallocatechingallate and - -epigallocatechin, into human plasma. Biosci Biotechnol Biochem.
Protective effects of green tea polyphenols and their major component, - -epigallocatechingallate EGCG , on 6-hydroxydopamine-induced apoptosis in PC12 cells. Redox Rep. Structural aspects of antioxidant activity of flavonoids. Protective effects of tea polyphenols against oxidative damage to red blood cells. Biochem Pharmacol. Flavonoid-based therapies in the early management of neurodegenerative diseases.
Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Orally administered epigallocatechin gallate attenuates retinal neuronal death in vivo and light-induced apoptosis in vitro. Brain Res. Stefanis L. Cold Spring Harb Perspect Med. J Neuroinflammation.
Neurochem Res. Appoptosin is a novel pro-apoptotic protein and mediates cell death in neurodegeneration. J Neurosci. Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol. Sadrzadeh SM, Saffari Y. Iron and brain disorders.
Am J Clin Pathol. Effects of natural antioxidants in neurodegenerative disease. Nutr Neurosci. Youdim MBH. Exp Neurobiol. Anti-inflammatory and anti-oxidative effects of the green tea polyphenol epigallocatechin gallate in human corneal epithelial cells. Mol Vis. Green tea compounds in breast cancer prevention and treatment. World J Clin Oncol. Green tea catechins and cardiovascular health: an update. Curr Med Chem.
Dietary polyphenols as potential nutraceuticals in management of diabetes: a review. J Diabetes Metab Disord. Novel insights of dietary polyphenols and obesity. Iron and alpha-synuclein in the substantia nigra of MPTP-treated mice: effect of neuroprotective drugs R-apomorphine and green tea polyphenol - -epigallocatechingallate.
J Mol Neurosci. The Biology of Alzheimer disease [Internet]. Potential protection of green tea polyphenols against intracellular amyloid beta-induced toxicity on primary cultured prefrontal cortical neurons of rats.
Neurosci Lett. Inhibition of acetylcholinesterase by green and white tea and their simulated intestinal metabolites. Food Funct. The green tea polyphenol - -epigallocatechin gallate attenuates beta-amyloid-induced neurotoxicity in cultured hippocampal neurons.
The green tea polyphenol - -epigallocatechin gallate prevents the aggregation of tau protein into toxic oligomers at substoichiometric ratios.
FEBS Lett. Epigallocatechingallate enhances clearance of phosphorylated tau in primary neurons. Long-term administration of green tea catechins improves spatial cognition learning ability in rats. J Nutr.
Agrawal M, Biswas A. Molecular diagnostics of neurodegenerative disorders. Front Mol Biosci. Green tea polyphenol - -epigallocatechingallate prevents N-methylphenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. Neuroprotection by - -epigallocatechingallate in a rat model of stroke is mediated through inhibition of endoplasmic reticulum stress.
Mol Med Rep. Epigallocatechingallate protects rat brain mitochondria against cadmium-induced damage. Food Chem Toxicol. Green tea epigallocatechin 3-gallate accumulates in mitochondria and displays a selective antiapoptotic effect against inducers of mitochondrial oxidative stress in neurons.
Shattuck lecture—Neurodegenerative diseases and prions. Surguchev A. Conformational diseases: Looking into the eyes. Brain Res. Breydo L. Westermark P. Influence of amyloid deposits on islet volume in maturity onset diabetes-mellitus. Gravina S. Amyloid-beta protein a-beta in alzheimers-disease brain—Biochemical and immunocytochemical analysis with antibodies specific for forms ending at a-beta or a-beta 43 J. Goetz C. Cold Spring Harb.
Dickson D. Lancet Neurol. Goedert M. Emamzadeh F. Uversky V. Neuropathology, biochemistry, and biophysics of alpha-synuclein aggregation. Brown D. Oligomeric alpha-synuclein and its role in neuronal death. Feldman A. Occupational exposure in parkinsonian disorders: A year prospective cohort study in men. Parkinsonism Relat. Dexter D. Alterations in the levels of iron, ferritin and other trace-metals in parkinsons-disease and other neurodegenerative diseases affecting the basal ganglia.
Barnham K. Hemmati-Dinarvand M. Jomova K. Metals, oxidative stress and neurodegenerative disorders. Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. EFSA J. Pall H. Raised cerebrospinal-fluid copper concentration in parkinsons-disease. Lovell M.
Hozumi I. Patterns of levels of biological metals in CSF differ among neurodegenerative diseases. Mahler A. Epigallocatechingallate: A useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?
EPMA J. Khan N. Targeting multiple signaling pathways by green tea polyphenol - -epigallocatechingallate. Cancer Res. Choi Y. The green tea polyphenol - -epigallocatechin gallate attenuates beta-amyloid-induced neurotoxicity in cultured hippocampal neurons. Life Sci. Mandel S. Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders. Food Res. Zhao J. RSC Adv. There is currently no clear dosage recommendation for EGCG, though mg daily for up to 4 weeks has been used safely in studies.
EGCG supplements have been linked to serious side effects and may interfere with medication absorption. EGCG is a powerful compound that may benefit health by reducing inflammation , aiding weight loss, and preventing certain chronic diseases. When taken as a supplement, EGCG has occasionally been associated with serious side effects.
The safest route is to consult with your healthcare provider prior to adding EGCG to your routine to ensure this supplement is right for you. This is a detailed article about green tea and its health benefits. Green tea is high in antioxidants that can improve the function of your body and…. Here is a detailed look at 10 evidence-based natural appetite suppressants that can help you lose weight.
Whether you dislike the taste, are trying to cut back on caffeine or just want something new, here are 9 delicious alternatives to coffee you should…. Thermogenic supplements are marketed as an easy way to burn fat, but people wonder if they really work.
This article reviews the most popular…. Both green and black tea are incredibly popular and associated with many health benefits. This article tells you whether green or black tea may be…. Green tea extract is a concentrated supplemental form of green tea. Here are 10 science-based benefits of green tea extract. Many studies show that green tea can help you lose weight. It contains bioactive substances that can make you burn more calories, even at rest. It's easy to make a quick breakfast from wholesome, nutritious foods.
Here are the 12 healthiest foods to eat in the morning.
0コメント