Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Aug. 30, 2021

Ribosome biogenesis and protein synthesis are fundamental rate-limiting steps for cell growth proliferation. The ribosomal proteins (RPs), comprising the structural parts of ribosome, essential ribosome assembly function. In addition to their canonical functions, multiple RPs have extra-ribosomal functions including activation p53-dependent or p53-independent pathways in response stress, resulting cycle arrest apoptosis. Defects biogenesis, translation, individual RPs, mutations been linked a diverse range human congenital disorders termed ribosomopathies. Ribosomopathies characterized by tissue-specific phenotypic abnormalities higher cancer risk later life. Recent discoveries somatic tumor types reinforce connections between defects cancer. this article, we review most recent advances understanding molecular consequences RP ribosomopathies We particularly discuss basis transition from hypo- hyper-proliferation with elevated risk, paradox "Dameshek's riddle." Furthermore, current treatments prospective therapies targeting defects. also highlight stress-based therapeutics. Importantly, insights into mechanisms resistance bring new perspectives susceptibility clinical implications therapy.

Language: Английский

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Bacterial Response to Oxidative Stress and RNA Oxidation

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 10, 2022

Bacteria have to cope with oxidative stress caused by distinct Reactive Oxygen Species (ROS), derived not only from normal aerobic metabolism but also oxidants present in their environments. The major ROS include superoxide O2-, hydrogen peroxide H2O2 and radical hydroxide HO•. To protect cells under stress, bacteria induce the expression of several genes, namely SoxRS, OxyR PerR regulons. Cells are able tolerate a certain number free radicals, high levels result oxidation biomolecules. Strikingly, RNA is particularly susceptible this common chemical damage. Oxidation causes formation strand breaks, elimination bases or insertion mutagenic lesions nucleobases. most modification 8-hydroxyguanosine (8-oxo-G), an oxidized form guanosine. structure function virtually all species (mRNA, rRNA, tRNA, sRNA) can be affected oxidation, leading translational defects harmful consequences for cell survival. However, evolved quality control pathways eliminate RNA, involving RNA-binding proteins like members MutT/Nudix family ribonuclease PNPase. Here we summarize current knowledge on bacterial response different responsible damage describe main strategies employed fight

Language: Английский

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Dual‐Responsive Nanocomposites for Synergistic Antibacterial Therapies Facilitating Bacteria‐Infected Wound Healing

Advanced Healthcare Materials, Journal Year: 2022, Volume and Issue: 12(6)

Published: Nov. 14, 2022

Abstract The rising dangers of bacterial infections have created an urgent need for the development a new generation antibacterial technologies and therapeutics. Antibacterial photodynamic therapy (PDT), considered as noninvasive treatment with no drug resistance, has become promising photochemistry‐involved strategy. Titanium oxide (TiO 2 ) is proved to be very efficient PDT agent among photosensitive materials, while property large bandgap TiO makes it only excited by ultraviolet light, which harmful organisms. In this work, novel ligand‐to‐metal charge transfer (LMCT) mediated strategy proposed via harmless near‐infrared light irradiation. By choosing mussel‐inspired material, polydopamine (PDA) involved in forming mesoporous @PDA nanoparticles (mTiO NPs). catechol groups PDA can attach tightly even colloidal environments, also form LMCT bridge, exciting exert function 808 nm Combining sonodynamic (SDT) photothermal properties PDA, simple structure mTiO enables synergistic applications multiple functions under dual excitation NIR ultrasound. This reliable all‐in‐one NPs achieve great effect rapid repair infected wounds.

Language: Английский

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Messenger RNA transport on lysosomal vesicles maintains axonal mitochondrial homeostasis and prevents axonal degeneration

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(6), P. 1087 - 1102

Published: April 10, 2024

Abstract In neurons, RNA granules are transported along the axon for local translation away from soma. Recent studies indicate that some of this transport involves hitchhiking on lysosome-related vesicles. present study, we leveraged ability to prevent these vesicles into by knockout lysosome–kinesin adaptor BLOC-one-related complex (BORC) identify a subset axonal mRNAs depend transport. We found BORC causes depletion large group mainly encoding ribosomal and mitochondrial/oxidative phosphorylation proteins. This results in mitochondrial defects eventually leads degeneration human induced pluripotent stem cell (iPSC)-derived mouse neurons. Pathway analyses depleted revealed mechanistic connection deficiency with common neurodegenerative disorders. These demonstrate mRNA is critical maintenance homeostasis its failure degeneration.

Language: Английский

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The Potential of Lactobacillus spp. for Modulating Oxidative Stress in the Gastrointestinal Tract

Antioxidants, Journal Year: 2020, Volume and Issue: 9(7), P. 610 - 610

Published: July 10, 2020

The gastrointestinal (GI) tract is crucial for food digestion and nutrient absorption in humans. However, the GI usually challenged with oxidative stress that can be induced by various factors, such as exogenous pathogenic microorganisms dietary alterations. As a part of gut microbiota, Lactobacillus spp. play an important role modulating cells tissues, especially tract. Oxidative linked excessive reactive oxygen species (ROS) formed few enzymes, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs). redox mechanisms may contribute to downregulation these ROS-forming enzymes. In addition, nuclear factor erythroid 2 (NFE2)-related (Nrf-2) kappa B (NF-κB) are two common transcription through which modulate well. closely associated inflammation certain diseases, could potentially applied early treatment amelioration either individually or together prebiotics. further research required revealing their action well extensive application future.

Language: Английский

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Antioxidant Defenses in the Human Eye: A Focus on Metallothioneins

Antioxidants, Journal Year: 2021, Volume and Issue: 10(1), P. 89 - 89

Published: Jan. 11, 2021

The human eye, the highly specialized organ of vision, is greatly influenced by oxidants endogenous and exogenous origin. Oxidative stress affects all structures eye with special emphasis on ocular surface, lens, retina its retinal pigment epithelium, which are considered natural barriers antioxidant protection, contributing to onset and/or progression diseases. These contain a complex defense system slightly different along depending cell tissue. In addition widely studied enzymatic antioxidants, including superoxide dismutase, glutathione peroxidase, catalase, peroxiredoxins selenoproteins, inter alia, metallothioneins (MTs) proteins growing interest further cell-mediated functions. This family cysteine rich low molecular mass captures neutralizes free radicals in redox-dependent mechanism involving zinc binding release. state art MTs, isoforms classification, main functions described date, Zn-MT redox cycle as system, activity Zn-MTs dependent number occupied zinc-binding sites, will be comprehensively reviewed.

Language: Английский

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Hepatoprotective Potential of Malaysian Medicinal Plants: A Review on Phytochemicals, Oxidative Stress, and Antioxidant Mechanisms

Molecules, Journal Year: 2022, Volume and Issue: 27(5), P. 1533 - 1533

Published: Feb. 24, 2022

Hepatotoxicity is a major global public health concern. Despite advances in modern medicine, the demerits of chemically prepared drugs outweigh their merits. In addition, treatment liver diseases based on medical principles has been found to produce several undesired side effects. Therefore, exploration medicinal plants gained worldwide attention for treating various diseases, including owing potential efficacy and cost effectiveness. Several plants, Andrographis paniculata, Bauhinia purpurea, Commelina nudiflora, Dillenia suffruticosa, Elaeis guineensis, Lygodium microphyllum, Nephrolepis biserrata, have reported with hepatoprotection. Moreover, these shown play vital role ameliorating cellular damage because they contain phytochemicals, alkaloids, saponins, flavonoids, tannins, terpenoids, steroids, polyphenols, diterpenoid lactones. The following antioxidant, anti-inflammatory, immunomodulatory, hepatoprotective compounds plants: andrographolide, rosmarinic acid, phenol, eugenol, 9,12-octadecadienoic, n-hexadecanoic dihydroxy dimethoxy flavone, sitosterol, demethoxycurcumin, quercetin, linoleic stigmasterol, kojic indole-2-one, α-terpinol, linalool, kaempferol, catechin, ellagic oleanolic acid. This paper aimed provide an in-depth review vivo studies Malaysian possessing properties, phytochemical ingredients, antioxidant mechanisms, emphasis species proven particularly useful hepatic disorders.

Language: Английский

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Comprehensive map of ribosomal 2′-O-methylation and C/D box snoRNAs in Drosophila melanogaster

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(6), P. 2848 - 2864

Published: Feb. 28, 2024

Abstract During their maturation, ribosomal RNAs (rRNAs) are decorated by hundreds of chemical modifications that participate in proper folding rRNA secondary structures and therefore function. Along with pseudouridine, methylation the 2′-hydroxyl ribose moiety (Nm) is most abundant modification rRNAs. The majority Nm eukaryotes placed Fibrillarin, a conserved methyltransferase belonging to ribonucleoprotein complex guided C/D box small nucleolar (C/D snoRNAs). These impact interactions between rRNAs, tRNAs mRNAs, some known fine tune translation rates efficiency. In this study, we built first comprehensive map sites Drosophila melanogaster rRNAs using two complementary approaches (RiboMethSeq Nanopore direct RNA sequencing) identified corresponding snoRNAs whole-transcriptome sequencing. We de novo 61 sites, from which 55 supported both sequencing methods, validated expression 106 predicted new or alternative targets for 31 them. Comparison level upon different stresses show only slight but specific variations, indicating relatively stable D. melanogaster. This study paves way investigate snoRNA-mediated 2′-O-methylation on proteostasis whole organism.

Language: Английский

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Temporal coordination of the transcription factor response to H2O2 stress

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 23, 2024

Abstract Oxidative stress from excess H 2 O activates transcription factors that restore redox balance and repair oxidative damage. Although many are activated by , it is unclear whether they at the same concentration, or time. Dose-dependent activation likely as not a singular state exhibits dose-dependent outcomes including cell-cycle arrest cell death. Here, we show factor both coordinated over Low levels of activate p53, NRF2 JUN. Yet under high these repressed, FOXO1, NF-κB, NFAT1 activated. Time-lapse imaging revealed order in which two groups depends on administered acutely bolus addition, continuously through glucose oxidase enzyme. Finally, provide evidence 2-Cys peroxiredoxins control group

Language: Английский

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ZNF574 is a quality control factor for defective ribosome biogenesis intermediates

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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