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Autophagy-Mediated Cellular Oxidative Stress Regulations

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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 8843

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Special Issue Editor

Dr. Valentina Cecarini

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Guest Editor

School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
Interests: autophagy; proteasome; Alzheimer’s disease; oxidation; enzyme regulation

Special Issue Information

Dear Colleagues,

Autophagy is a dynamic catabolic process playing a central role in maintaining cellular homeostasis. Through the autophagic pathway, cells degrade and recycle unnecessary or dysfunctional cytoplasmic components, including proteins and damaged organelles. Autophagy can be activated in response to diverse stressors such as nutrient deprivation, hypoxia, drugs and virus-mediated infections. A growing amount of evidence in recent years indicates for autophagy a role as a crucial mediator in the regulation of oxidative stress response. Oxidative stress is the result of the activity of both reactive oxygen species (ROS) and reactive nitrogen species (RNS) mainly produced through oxygen metabolism in mitochondria. ROS/RNS at physiological levels act as signalling molecules that regulate numerous cellular conditions whereas an excessive production can eventually cause cell death and give rise to a variety of diseases. In addition, high levels of oxidative stress can dysregulate autophagy favouring the accumulation of harmful aggregates. Thus, a complex interplay exists between these two processes that still remains unclear.

This Special Issue aims to collect research articles and reviews that deeply dissect and try to unravel the exact mechanisms that regulate the relationship between autophagy and oxidative stress, highlighting the role of mediators of this crosstalk and the correlations with disorders and aging.

Dr. Valentina Cecarini
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

oxidative stress
reactive oxygen species
autophagy
aging
proteolysis

Published Papers (5 papers)

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Research

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14 pages, 3871 KiB

Open AccessArticle

Ginsenosides Rg1 and Rg2 Activate Autophagy and Attenuate Oxidative Stress in Neuroblastoma Cells Overexpressing Aβ(1-42)

by Ziqi Liu, Valentina Cecarini, Massimiliano Cuccioloni, Laura Bonfili, Chunmei Gong, Mauro Angeletti and Anna Maria Eleuteri

Antioxidants 2024, 13(3), 310; https://doi.org/10.3390/antiox13030310 - 1 Mar 2024

Viewed by 844

Abstract

Alzheimer’s disease is a neurodegeneration with protein deposits, altered proteolysis, and inflammatory and oxidative processes as major hallmarks. Despite the continuous search for potential therapeutic treatments, no cure is available to date. The use of natural molecules as adjuvants in the treatment of Alzheimer’s disease is a very promising strategy. In this regard, ginsenosides from ginseng root show a variety of biological effects. Here, we dissected the role of ginsenosides Rg1 and Rg2 in modulating autophagy and oxidative stress in neuroblastoma cells overexpressing Aβ(1-42). Key hallmarks of these cellular processes were detected through immunomethods and fluorometric assays. Our findings indicate that ginsenosides are able to upregulate autophagy in neuronal cells as demonstrated by increased levels of LC3II and Beclin-1 proteins and decreased amounts of p62. Simultaneously, an activation of lysosomal hydrolases was observed. Furthermore, autophagy activation promoted the clearance of Aβ(1-42). Rg1 and Rg2 also reduced oxidative stress sources and macromolecule oxidation, promoting NRF2 nuclear translocation and the expression of antioxidant enzymes. Our data further clarify the mechanisms of action of Rg1 and Rg2, indicating new insights into their role in the management of disorders like Alzheimer’s disease. Full article

(This article belongs to the Special Issue Autophagy-Mediated Cellular Oxidative Stress Regulations)

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26 pages, 9712 KiB

Open AccessArticle

SIRT5 Activation and Inorganic Phosphate Binding Reduce Cancer Cell Vitality by Modulating Autophagy/Mitophagy and ROS

by Federica Barreca, Michele Aventaggiato, Laura Vitiello, Luigi Sansone, Matteo Antonio Russo, Antonello Mai, Sergio Valente and Marco Tafani

Antioxidants 2023, 12(8), 1635; https://doi.org/10.3390/antiox12081635 - 18 Aug 2023

Cited by 3 | Viewed by 1369

Abstract

Cancer cells show increased glutamine consumption. The glutaminase (GLS) enzyme controls a limiting step in glutamine catabolism. Breast tumors, especially the triple-negative subtype, have a high expression of GLS. Our recent study demonstrated that GLS activity and ammonia production are inhibited by sirtuin 5 (SIRT5). We developed MC3138, a selective SIRT5 activator. Treatment with MC3138 mimicked the deacetylation effect mediated by SIRT5 overexpression. Moreover, GLS activity was regulated by inorganic phosphate (Pi). Considering the interconnected roles of GLS, SIRT5 and Pi in cancer growth, our hypothesis is that activation of SIRT5 and reduction in Pi could represent a valid antitumoral strategy. Treating cells with MC3138 and lanthanum acetate, a Pi chelator, decreased cell viability and clonogenicity. We also observed a modulation of MAP1LC3B and ULK1 with MC3138 and lanthanum acetate. Interestingly, inhibition of the mitophagy marker BNIP3 was observed only in the presence of MC3138. Autophagy and mitophagy modulation were accompanied by an increase in cytosolic and mitochondrial reactive oxygen species (ROS). In conclusion, our results show how SIRT5 activation and/or Pi binding can represent a valid strategy to inhibit cell proliferation by reducing glutamine metabolism and mitophagy, leading to a deleterious accumulation of ROS. Full article

(This article belongs to the Special Issue Autophagy-Mediated Cellular Oxidative Stress Regulations)

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14 pages, 3822 KiB

Open AccessArticle

Glucose Starvation-Caused Oxidative Stress Induces Inflammation and Autophagy in Human Gingival Fibroblasts

by Runbo Li, Hirohito Kato, Yoichiro Taguchi, Xin Deng, Emika Minagawa, Takaya Nakata and Makoto Umeda

Antioxidants 2022, 11(10), 1907; https://doi.org/10.3390/antiox11101907 - 26 Sep 2022

Cited by 8 | Viewed by 2160

Abstract

Gingival tissue experiences an environment of nutrient shortage, such as low glucose conditions, after periodontal surgery. Our previous studies found that this low glucose condition inhibits normal gingival cell functions. However, the mechanism by which this glucose-deficient environment causes cellular damage to human gingival fibroblasts (HGnFs) remains unclear. This study aimed to investigate the biological effects of ROS induction on HGnFs under low glucose conditions. ROS levels and cellular anti-ROS ability of HGnFs under different glucose concentrations were evaluated by measuring ROS formation and the expression of superoxide dismutase and heme oxygenase 1. Changes in cellular viability were investigated using 5-bromo-2′-deoxyuridine assay and cell survival detection, and the cellular damage was evaluated by the expression of inflammatory cytokines and changes in the expression of autophagy-related protein. ROS formation was then blocked using N-acetyl-L-cysteine (NAC), and the effects of ROS on HGnFs under low glucose conditions were investigated. Low glucose conditions induced ROS accumulation, reduced cellular activity, and induced inflammation and autophagy. After NAC application, the anti-ROS capacity increased, cellular activity improved, and inflammation and autophagy were controlled. This can be effectively controlled by the application of antioxidants such as NAC. Full article

(This article belongs to the Special Issue Autophagy-Mediated Cellular Oxidative Stress Regulations)

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15 pages, 6677 KiB

Open AccessArticle

Physapruin A Induces Reactive Oxygen Species to Trigger Cytoprotective Autophagy of Breast Cancer Cells

by Tzu-Jung Yu, Jun-Ping Shiau, Jen-Yang Tang, Chia-Hung Yen, Ming-Feng Hou, Yuan-Bin Cheng, Chih-Wen Shu and Hsueh-Wei Chang

Antioxidants 2022, 11(7), 1352; https://doi.org/10.3390/antiox11071352 - 11 Jul 2022

Cited by 6 | Viewed by 1781

Abstract

Physalis peruviana-derived physapruin A (PHA) is a potent compound that selectively generates reactive oxygen species (ROS) and induces cancer cell death. Autophagy, a cellular self-clearance pathway, can be induced by ROS and plays a dual role in cancer cell death. However, the role of autophagy in PHA-treated cancer cells is not understood. Our study initially showed that autophagy inhibitors such as bafilomycin A1 enhanced the cytotoxic effects of PHA in breast cancer cell lines, including MCF7 and MDA-MB-231. PHA treatment decreased the p62 protein level and increased LC3-II flux. PHA increased the fluorescence intensity of DAPGreen and DALGreen, which are used to reflect the formation of autophagosome/autolysosome and autolysosome, respectively. ROS scavenger N-acetylcysteine (NAC) decreased PHA-elevated autophagy activity, implying that PHA-induced ROS may be required for autophagy induction in breast cancer cells. Moreover, the autophagy inhibitor increased ROS levels and enhanced PHA-elevated ROS levels, while NAC scavenges the produced ROS resulting from PHA and autophagy inhibitor. In addition, the autophagy inhibitor elevated the PHA-induced proportion of annexin V/7-aminoactinmycin D and cleavage of caspase-3/8/9 and poly (ADP-ribose) polymerase. In contrast, NAC and apoptosis inhibitor Z-VAD-FMK blocked the proportion of annexin V/7-aminoactinmycin D and the activation of caspases. Taken together, PHA induced ROS to promote autophagy, which might play an antioxidant and anti-apoptotic role in breast cancer cells. Full article

(This article belongs to the Special Issue Autophagy-Mediated Cellular Oxidative Stress Regulations)

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Review

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28 pages, 2452 KiB

Open AccessReview

Autophagy Activation Promoted by Pulses of Light and Phytochemicals Counteracting Oxidative Stress during Age-Related Macular Degeneration

by Roberto Pinelli, Michela Ferrucci, Francesca Biagioni, Caterina Berti, Violet Vakunseth Bumah, Carla Letizia Busceti, Stefano Puglisi-Allegra, Gloria Lazzeri, Alessandro Frati and Francesco Fornai

Antioxidants 2023, 12(6), 1183; https://doi.org/10.3390/antiox12061183 - 30 May 2023

Cited by 1 | Viewed by 1953

Abstract

The seminal role of autophagy during age-related macular degeneration (AMD) lies in the clearance of a number of reactive oxidative species that generate dysfunctional mitochondria. In fact, reactive oxygen species (ROS) in the retina generate misfolded proteins, alter lipids and sugars composition, disrupt DNA integrity, damage cell organelles and produce retinal inclusions while causing AMD. This explains why autophagy in the retinal pigment epithelium (RPE), mostly at the macular level, is essential in AMD and even in baseline conditions to provide a powerful and fast replacement of oxidized molecules and ROS-damaged mitochondria. When autophagy is impaired within RPE, the deleterious effects of ROS, which are produced in excess also during baseline conditions, are no longer counteracted, and retinal degeneration may occur. Within RPE, autophagy can be induced by various stimuli, such as light and naturally occurring phytochemicals. Light and phytochemicals, in turn, may synergize to enhance autophagy. This may explain the beneficial effects of light pulses combined with phytochemicals both in improving retinal structure and visual acuity. The ability of light to activate some phytochemicals may further extend such a synergism during retinal degeneration. In this way, photosensitive natural compounds may produce light-dependent beneficial antioxidant effects in AMD. Full article

(This article belongs to the Special Issue Autophagy-Mediated Cellular Oxidative Stress Regulations)

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