L-amino acid oxidases: properties and molecular mechanisms of action

During previous decade L-amino acid oxidases (LAAO) attracted the steady interest of researchers due to their poly functional effects on different biological systems. The review summarizes information concerning the sources, structure, phisico-chemical and catalytical properties of LAAO which exhibit antibacterial, antifungal, antiprotozoal, antiviral effects as well as the ambiguous action on platelet aggregation. Special attention is devoted to the elucidation of molecular mechanisms of LAAO action. It is proposed that the unique properties of LAAO are based on their catalytic reaction, which causes the decrease of L-amino acid levels, including the essential amino acids and formation of hydrogen peroxide. The action of liberated H2O2 on cells involves the synthesis of oxygen reactive species and the development of necrotic and apoptotic pathways of cell death. The presence of carbohydrate moieties in LAAO molecules promotes their attachment to cell's surface and creation of high H2O2 local concentrations. The wide range of LAAO biological effects is undoubtedly connected with their important functional roles in the organism. In particular, it was shown that in the mice brain the LAAO-catalyzed reaction is the single pathway of L-lysine degradation, while in the mice milk LAAO carry out the antibacterial effect and in human leucocytes LAAO take part in fulfilling their defending role. Protector action may be also attributed to the oxidases from the other numerous sources: microscopic fungi, snake venoms and sea inhabitants.

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Pleiotropic Biological Effects of Dietary Phenolic Compounds and their Metabolites on Energy Metabolism, Inflammation and Aging

Molecules ◽

10.3390/molecules25030596 ◽

2020 ◽

Vol 25 (3) ◽

pp. 596 ◽

Cited By ~ 3

Author(s):

María del Carmen Villegas-Aguilar ◽

Álvaro Fernández-Ochoa ◽

María de la Luz Cádiz-Gurrea ◽

Sandra Pimentel-Moral ◽

Jesús Lozano-Sánchez ◽

...

Keyword(s):

Energy Metabolism ◽

Phenolic Compounds ◽

Molecular Mechanisms ◽

Biological Effects ◽

Biological Properties ◽

In Vivo Studies ◽

Wide Range ◽

High Prevalence

Dietary phenolic compounds are considered as bioactive compounds that have effects in different chronic disorders related to oxidative stress, inflammation process, or aging. These compounds, coming from a wide range of natural sources, have shown a pleiotropic behavior on key proteins that act as regulators. In this sense, this review aims to compile information on the effect exerted by the phenolic compounds and their metabolites on the main metabolic pathways involved in energy metabolism, inflammatory response, aging and their relationship with the biological properties reported in high prevalence chronic diseases. Numerous in vitro and in vivo studies have demonstrated their pleiotropic molecular mechanisms of action and these findings raise the possibility that phenolic compounds have a wide variety of roles in different targets.

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The N-Terminal 24 Amino Acids of the p55 Gamma Regulatory Subunit of Phosphoinositide 3-Kinase Binds Rb and Induces Cell Cycle Arrest

Molecular and Cellular Biology ◽

10.1128/mcb.23.5.1717-1725.2003 ◽

2003 ◽

Vol 23 (5) ◽

pp. 1717-1725 ◽

Cited By ~ 50

Author(s):

Xianmin Xia ◽

Aiwu Cheng ◽

Damilola Akinmade ◽

Anne W. Hamburger

Keyword(s):

Cell Cycle ◽

Amino Acid ◽

Cell Cycle Arrest ◽

Cell Cycle Progression ◽

Molecular Mechanisms ◽

Biological Effects ◽

Cycle Progression ◽

Regulatory Subunits ◽

Cycle Arrest ◽

Phosphoinositide 3 Kinase

ABSTRACT Although phosphoinositide 3-kinase (PI 3-kinase) is essential for cell cycle progression, the molecular mechanisms that regulate its diverse biological effects are poorly understood. We demonstrate here that Rb, a key regulator of cell cycle progression, associates with p55 kDa (p55α and p55γ) regulatory subunits of PI 3-kinase in vivo and in vitro. Both confocal microscopy and biochemical analysis demonstrated the presence of p55γ in the nucleus. The 24-amino-acid N-terminal end of p55γ, which is unique among PI 3-kinase regulatory subunits, was sufficient to bind Rb. Addition of serum or growth factors to quiescent cells triggered the dissociation of Rb from p55. Ectopic expression of the 24-amino-acid N-terminal end of p55γ inhibited cell cycle progression, as evidenced by induction of cell growth arrest at the G0/G1 phase, inhibition of DNA synthesis, inhibition of cyclin D and cyclin E promoter activity, and changes in the expression of cell cycle-related proteins. The inhibitory effects of the N-terminal end of p55γ on cell cycle progression depended on the presence of functional Rb. These data demonstrate for the first time an association of p55γ with Rb and show that modification of this association can lead to cell cycle arrest.

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Amino acid limitation regulates gene expression

Proceedings of The Nutrition Society ◽

10.1017/s0029665199000828 ◽

1999 ◽

Vol 58 (3) ◽

pp. 625-632 ◽

Cited By ~ 29

Author(s):

Alain Bruhat ◽

Céline Jousse ◽

Pierre Fafournoux

Keyword(s):

Gene Expression ◽

Amino Acids ◽

Amino Acid ◽

Molecular Mechanisms ◽

Binding Protein ◽

Regulation Of Gene Expression ◽

Essential Amino Acids ◽

Mrna Levels ◽

Dependent Manner ◽

Control Of Gene Expression

In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0·0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.

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Mechanisms and functions of p38 MAPK signalling

Biochemical Journal ◽

10.1042/bj20100323 ◽

2010 ◽

Vol 429 (3) ◽

pp. 403-417 ◽

Cited By ~ 865

Author(s):

Ana Cuadrado ◽

Angel R. Nebreda

Keyword(s):

P38 Mapk ◽

Molecular Mechanisms ◽

Biological Effects ◽

Mitogen Activated Protein Kinase ◽

Wide Range ◽

Mapk Signalling ◽

Mitogen Activated Protein ◽

External Signals ◽

Protein Kinase Signalling ◽

Genetic Mouse Models

The p38 MAPK (mitogen-activated protein kinase) signalling pathway allows cells to interpret a wide range of external signals and respond appropriately by generating a plethora of different biological effects. The diversity and specificity in cellular outcomes is achieved with an apparently simple linear architecture of the pathway, consisting of a core of three protein kinases acting sequentially. In the present review, we dissect the molecular mechanisms underlying p38 MAPK functions, with special emphasis on the activation and regulation of the core kinases, the interplay with other signalling pathways and the nature of p38 MAPK substrates as a source of functional diversity. Finally, we discuss how genetic mouse models are facilitating the identification of physiological functions for p38 MAPKs, which may impinge on their eventual use as therapeutic targets.

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Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000485395 ◽

2017 ◽

Vol 44 (3) ◽

pp. 948-966 ◽

Cited By ~ 28

Author(s):

Tesfaye Worku ◽

Dinesh Bhattarai ◽

Duncan Ayers ◽

Kai Wang ◽

Chen Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Gene Regulation ◽

Molecular Mechanisms ◽

Future Directions ◽

Diagnostic Biomarkers ◽

Functional Roles ◽

Gene Therapies ◽

Wide Range ◽

Recent Developments ◽

Non Coding Rnas

Long non-coding RNAs (lncRNAs), a class of non-coding transcripts, have recently been emerging with heterogeneous molecular actions, adding a new layer of complexity to gene-regulation networks in tumorigenesis. LncRNAs are considered important factors in several ovarian cancer histotypes, although few have been identified and characterized. Owing to their complexity and the lack of adapted molecular technology, the roles of most lncRNAs remain mysterious. Some lncRNAs have been reported to play functional roles in ovarian cancer and can be used as classifiers for personalized medicine. The intrinsic features of lncRNAs govern their various molecular mechanisms and provide a wide range of platforms to design different therapeutic strategies for treating cancer at a particular stage. Although we are only beginning to understand the functions of lncRNAs and their interactions with microRNAs (miRNAs) and proteins, the expanding literature indicates that lncRNA-miRNA interactions could be useful biomarkers and therapeutic targets for ovarian cancer. In this review, we discuss the genetic variants of lncRNAs, heterogeneous mechanisms of actions of lncRNAs in ovarian cancer tumorigenesis, and drug resistance. We also highlight the recent developments in using lncRNAs as potential prognostic and diagnostic biomarkers. Lastly, we discuss potential approaches for linking lncRNAs to future gene therapies, and highlight future directions in the field of ovarian cancer research.

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Nutrient Responsive O-GlcNAcylation Dynamically Modulates Galectin 3 Secretion

10.1101/2021.04.05.438483 ◽

2021 ◽

Author(s):

Mohit P Mathew ◽

Julie G Donaldson ◽

John A. Hanover

Keyword(s):

Cell Surface ◽

Disease Progression ◽

Molecular Mechanisms ◽

Biological Effects ◽

Nutrient Sensing ◽

Functional Roles ◽

Disease States ◽

Terminal Galactose ◽

Significant Difference ◽

Galectin 3

Endomembrane glycosylation and cytoplasmic O-GlcNAcylation each play essential roles in nutrient sensing, and in fact, characteristic changes in glycan patterns have been described in disease states such as diabetes and cancer. These changes in glycosylation have important functional roles and can drive disease progression. However, little is known about the molecular mechanisms underlying how these signals are integrated and transduced into biological effects. Galectins are proteins that bind glycans that are secreted by a poorly characterized non-classical secretory mechanism. Once outside the cell, galectins bind to terminal galactose residues of cell surface glycans and modulate numerous extracellular functions like clathrin independent endocytosis (CIE). Originating in the cytoplasm, galectins are predicted substrates for O-GlcNAc addition and removal. This study shows that galectin 3 is O-GlcNAcylated, and that changes in O-GlcNAc cycling alters its secretion. Moreover, we determined that there is a significant difference in O-GlcNAcylation status between cytoplasmic and secreted galectin 3. We observed dramatic alterations in galectin 3 secretion in response to nutrient conditions and that these changes were dependent on dynamic O-GlcNAcylation. Finally, we showed that alterations in galectin 3 secretion via disrupted O-GlcNAcylation drove changes in CIE. These results indicate that dynamic O-GlcNAcylation of galectin 3 plays a role in modulating its secretion and can tune its function of transducing nutrient sensing information coded in cell surface glycosylation into biological effects.

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AMINO ACID COMPOSITION OF STEVIA RAW MATERIALS OF DIFFERENT ORIGIN

chemistry of plant raw material ◽

10.14258/jcprm.2021017695 ◽

2021 ◽

pp. 113-119

Author(s):

Evgeny Evgenievich Kurdyukov ◽

Elena Fedorovna Semenova ◽

Ol'ga Aleksandrovna Vodopyanova ◽

Yakov Petrovich Moiseev ◽

Olesya Petrovna Rodina ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Amino Acid Composition ◽

Acid Composition ◽

Raw Materials ◽

Stevia Rebaudiana ◽

Essential Amino Acids ◽

Stevia Rebaudiana Bertoni ◽

Wide Range ◽

The Republic

Dried stevia leaves (Stevia rebaudiana Bertoni) were used as objects of research. We studied the leaves of stevia varieties Ramon sweetener grown in the Penza region, the leaves of stevia varieties Ramon sweetener grown in the Tver region, Krasnodar region, the Republic of Crimea, as well as imported raw stevia from India and Paraguay. The purpose of this work is a comparative study of the amino acid composition of raw stevia grown in different conditions. The amino acid composition of stevia leaves (Stevia rebaudiana Bertoni) was revealed by capillary electrophoresis.13 amino acids were identified, of which eight are "essential" (lysine, phenylalanine, histidine, leucine, isoleucine, methionine, valine, threonine). The proportion of essential amino acids in stevia raw materials ranged from 2.99 to 4.64%. The content of interchangeable acids was: tyrosine from 0.24% to 0.36%, Proline from 0.44 to 0.68%, serine from 0.77 to 1.03%, alanine from 0.48 to 0.83%, glycine from 0.40 to 0.68%. The total amount of amino acids detected is higher in the Ramon sweetener variety grown in the Penza region (9.52%) compared to other samples, the lowest amount is found in stevia grown in Paraguay (6.46%). The results obtained indicate the prospects for further studies of the amino acid composition of Stevia rebaudiana and can characterize this species as a source of valuable medicinal substances with a wide range of pharmacological activity.

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Extracellular Microvesicles (MV’s) Isolated from 5-Azacytidine-and-Resveratrol-Treated Cells Improve Viability and Ameliorate Endoplasmic Reticulum Stress in Metabolic Syndrome Derived Mesenchymal Stem Cells

Stem Cell Reviews and Reports ◽

10.1007/s12015-020-10035-4 ◽

2020 ◽

Vol 16 (6) ◽

pp. 1343-1355

Author(s):

C Weiss ◽

K Kornicka-Grabowska ◽

M Mularczyk ◽

N Siwinska ◽

K Marycz

Keyword(s):

Metabolic Syndrome ◽

Stem Cells ◽

Endoplasmic Reticulum ◽

Mesenchymal Stem Cells ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Biological Effects ◽

Cell Types ◽

Wide Range ◽

Proper Functions

AbstractExtracellular vesicles (EVs), a spherical membrane fragments including exosomes, are released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. As MVs cargo include DNA, RNA, miRNA, lipids and proteins their have gain special attention in the field of regenerative medicine. Depending on the type of transferred molecules, MVs may exert wide range of biological effects in recipient cells including pro-inflammatory and anti-apoptotic action. In presented paper, we isolated MVs form adipose derived mesenchymal stem cells (ASC) which underwent stimulation with 5-azacytydine and resveratrol (AZA/RES) in order to improve their therapeutic potential. Then, isolated MVs were applied to ASC with impaired cytophysiological properties, isolated from equine metabolic syndrome diagnosed animals. Using RT-PCR, immunofluorescence, ELISA, confocal microscopy and western blot, we have evaluated the effects of MVs on recipient cells. We have found, that MVs derived from AZA/RES treated ASC ameliorates apoptosis, senescence and endoplasmic reticulum (ER) stress in deteriorated cells, restoring their proper functions. The work indicates, that cells treated with AZA/RES through their paracrine action can rejuvenate recipient cells. However, further research needs to be performed in order to fully understand the molecular mechanisms of these bioactive factors action.

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Antiviral Properties of Flavonoids and Delivery Strategies

Nutrients ◽

10.3390/nu12092534 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2534 ◽

Cited By ~ 2

Author(s):

Paolino Ninfali ◽

Antonella Antonelli ◽

Mauro Magnani ◽

Emanuele Salvatore Scarpa

Keyword(s):

Molecular Mechanisms ◽

Viral Infections ◽

Biological Effects ◽

Antiviral Agents ◽

Synthetic Drugs ◽

Antiviral Therapies ◽

Antiviral Effects ◽

Wide Range ◽

Antiviral Activities ◽

Delivery Strategies

This review summarizes the latest advancements in phytochemicals as functional antiviral agents. We focused on flavonoids, like apigenin, vitexin, quercetin, rutin and naringenin, which have shown a wide range of biological effects including antiviral activities. The molecular mechanisms of their antiviral effects mainly consist in the inhibition of viral neuraminidase, proteases and DNA/RNA polymerases, as well as in the modification of various viral proteins. Mixtures of different flavonoids or combination of flavonoids with antiviral synthetic drugs provide an enhancement of their antiviral effects. Recent strategies in drug delivery significantly contribute to overcoming the low bioavailability of flavonoids. Frequent viral infections worldwide have led to the need for new effective antiviral agents, which can be identified among the various phytochemicals. In this light, screening the antiviral activities of a cocktail of flavonoids would be advantageous in order to prevent viral infections and improve current antiviral therapies.

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Embryotoxic and Teratogenic Effects of Gamma Radiation on Zebrafish (Danio rerio)

Medical Radiology and radiation safety ◽

10.12737/1024-6177-2020-65-6-11-16 ◽

2021 ◽

Vol 65 (6) ◽

pp. 11-16

Author(s):

D Isaev ◽

D. Guryev ◽

T. Blohina ◽

E. Yashkina ◽

A. Osipov

Keyword(s):

Ionizing Radiation ◽

Danio Rerio ◽

Molecular Mechanisms ◽

Biological Effects ◽

Radiation Risk ◽

Teratogenic Effects ◽

Dose Rates ◽

Wide Range ◽

Radiation Induced ◽

Acute And Chronic Effects

The review considers investigations presenting experimental data on the embryotoxic and teratogenic effects of exposure to ionizing radiation in zebrafish (Danio rerio) which is a convenient model for experimental embryology and radiation biology. The molecular mechanisms involved in response to the ionizing radiation influence as well as determining the embryonic death level, development disorders of embryos are examined. The data on acute and chronic effects of ionizing radiation on embryos of various stages of development with wide range of dose rates are presented. It was shown that the influence of γ-radiation on the death and development of zebrafish embryos is nonmonotonic and depends both on the irradiation conditions and on the stage of embryogenesis. The results of such studies are extremely important for understanding the mechanisms of radiation-induced biological effects formation in the embryogenesis of vertebrates, including humans, as well as for developing methods and approaches to assessing radiation risk for a developing organism.

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