Correction: A Computational Exploration of the Interactions of the Green Tea Polyphenol (–)-Epigallocatechin 3-Gallate with Cardiac Muscle Troponin C

Botten, Dominic; Fugallo, Giorgia; Fraternali, Franca; Molteni, Carla

doi:10.1371/annotation/23964dab-0e50-4644-b3b1-7c9e4ee09958

Cited by 3 publications

(1 citation statement)

References 43 publications

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“…Although structural determinations of ligand binding (EGCG, W-7) to troponin subunits have been made, most studies have involved binary complexes (TnI and TnC) and partial sequences (Robertson et al, 2010;Botten et al, 2013;Hwang and Sykes, 2015). Recent molecular dynamics simulations have emphasized the importance of studying the intact troponin core with TnI, TnC, and TnT present (Papadaki and Marston, 2016;Zamora et al, 2016).…”

Section: Troponin Structural Correlationsmentioning

confidence: 99%

Molecular defects in cardiac myofilament Ca2+- regulation due to cardiomyopathy-linked mutations can be reversed by small molecules binding to troponin

Sheehan

Messer

Papadaki

et al. 2018

Journal of Molecular and Cellular Cardiology

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Section: Troponin Structural Correlationsmentioning

confidence: 99%

Molecular defects in cardiac myofilament Ca2+- regulation due to cardiomyopathy-linked mutations can be reversed by small molecules binding to troponin

Sheehan

Messer

Papadaki

et al. 2018

Journal of Molecular and Cellular Cardiology

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Gallic Acid Regulates Skin Photoaging in UVB‐exposed Fibroblast and Hairless Mice

Hwang

Park

Lee

et al. 2014

Phytotherapy Research

129

102

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Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin-6, and MMP-1 were significantly suppressed, and type I procollagen expression was stimulated in UVB-irradiated and GA-treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP-1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor-β1. Our data indicate that GA is a potential candidate for the prevention of UVB-induced premature skin aging.

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Molecular Defects in Cardiac Myofilament Ca2+-Regulation Due to Cardiomyopathy-Linked Mutations Can Be Reversed by Small Molecules Binding to Troponin

et al. 2018

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The inherited cardiomyopathies, hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are relatively common, potentially life-threatening and currently untreatable. Mutations are often in the contractile proteins of cardiac muscle and cause abnormal Ca2+ regulation via troponin. HCM is usually linked to higher myofilament Ca2+-sensitivity whilst in both HCM and DCM mutant tissue there is often an uncoupling of the relationship between troponin I (TnI) phosphorylation by PKA and modulation of myofilament Ca2+-sensitivity, essential for normal responses to adrenaline. The adrenergic response is blunted, and this may predispose the heart to failure under stress. At present there are no compounds or interventions that can prevent or treat sarcomere cardiomyopathies. There is a need for novel therapies that act at a more fundamental level to affect the disease process. We demonstrated that epigallocatechin-3 gallate (EGCG) was found to be capable of restoring the coupled relationship between Ca2+-sensitivity and TnI phosphorylation in mutant thin filaments to normal in vitro, independent of the mutation (15 mutations tested). We have labeled this property “re-coupling.” The action of EGCG in vitro to reverse the abnormality caused by myopathic mutations would appear to be an ideal pharmaceutical profile for treatment of inherited HCM and DCM but EGCG is known to be promiscuous in vivo and is thus unsuitable as a therapeutic drug. We therefore investigated whether other structurally related compounds can re-couple myofilaments without these off-target effects. We used the quantitative in vitro motility assay to screen 40 compounds, related to C-terminal Hsp90 inhibitors, and found 23 that can re-couple mutant myofilaments. There is no correlation between re-couplers and Hsp90 inhibitors. The Ca2+-sensitivity shift due to TnI phosphorylation was restored to 2.2 ± 0.01-fold (n = 19) compared to 2.0 ± 0.24-fold (n = 7) in wild-type thin filaments. Many of these compounds were either pure re-couplers or pure desensitizers, indicating these properties are independent; moreover, re-coupling ability could be lost with small changes of compound structure, indicating the possibility of specificity. Small molecules that can re-couple may have therapeutic potential.HIGHLIGHTS - Inherited cardiomyopathies are common diseases that are currently untreatable at a fundamental level and therefore finding a small molecule treatment is highly desirable.- We have identified a molecular level dysfunction common to nearly all mutations: uncoupling of the relationship between troponin I phosphorylation and modulation of myofilament Ca2+-sensitivity, essential for normal responses to adrenaline.- We have identified a new class of drugs that are capable of both reducing Ca2+-sensitivity and/or recouping the relationship between troponin I phosphorylation and Ca2+-sensitivity.- The re-coupling phenomenon can be explained on the basis of a single mechanism that is testable.- Measurements with a wide range of small molecules of varyi...

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Correction: A Computational Exploration of the Interactions of the Green Tea Polyphenol (–)-Epigallocatechin 3-Gallate with Cardiac Muscle Troponin C

Cited by 3 publications

References 43 publications

Molecular defects in cardiac myofilament Ca2+- regulation due to cardiomyopathy-linked mutations can be reversed by small molecules binding to troponin

Molecular defects in cardiac myofilament Ca2+- regulation due to cardiomyopathy-linked mutations can be reversed by small molecules binding to troponin

Gallic Acid Regulates Skin Photoaging in UVB‐exposed Fibroblast and Hairless Mice

Molecular Defects in Cardiac Myofilament Ca2+-Regulation Due to Cardiomyopathy-Linked Mutations Can Be Reversed by Small Molecules Binding to Troponin

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