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Oxidative Medicine and Cellular... 2019
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Oxidative Medicine and Cellular... 2020Mitochondria are the main organelles that produce adenosine 5'-triphosphate (ATP) and reactive oxygen species (ROS) in eukaryotic cells and meanwhile susceptible to... (Review)
Review
Mitochondria are the main organelles that produce adenosine 5'-triphosphate (ATP) and reactive oxygen species (ROS) in eukaryotic cells and meanwhile susceptible to oxidative damage. The irreversible oxidative damage in mitochondria has been implicated in various human diseases. Increasing evidence indicates the therapeutic potential of mitochondria-targeted antioxidants (MTAs) for oxidative damage-associated diseases. In this article, we introduce the advantageous properties of MTAs compared with the conventional (nontargeted) ones, review different mitochondria-targeted delivery systems and antioxidants, and summarize their experimental results for various disease treatments in different animal models and clinical trials. The combined evidence demonstrates that mitochondrial redox homeostasis is a potential target for disease treatment. Meanwhile, the limitations and prospects for exploiting MTAs are discussed, which might pave ways for further trial design and drug development.
Topics: Animals; Antioxidants; Drug Delivery Systems; Humans; Mitochondria; Oxidation-Reduction
PubMed: 33354280
DOI: 10.1155/2020/8837893 -
Cellular and Molecular Life Sciences :... Mar 2015Laccases are part of the family of multicopper oxidases (MCOs), which couple the oxidation of substrates to the four electron reduction of O2 to H2O. MCOs contain a... (Review)
Review
Laccases are part of the family of multicopper oxidases (MCOs), which couple the oxidation of substrates to the four electron reduction of O2 to H2O. MCOs contain a minimum of four Cu's divided into Type 1 (T1), Type 2 (T2), and binuclear Type 3 (T3) Cu sites that are distinguished based on unique spectroscopic features. Substrate oxidation occurs near the T1, and electrons are transferred approximately 13 Å through the protein via the Cys-His pathway to the T2/T3 trinuclear copper cluster (TNC), where dioxygen reduction occurs. This review outlines the electron transfer (ET) process in laccases, and the mechanism of O2 reduction as elucidated through spectroscopic, kinetic, and computational data. Marcus theory is used to describe the relevant factors which impact ET rates including the driving force, reorganization energy, and electronic coupling matrix element. Then, the mechanism of O2 reaction is detailed with particular focus on the intermediates formed during the two 2e(-) reduction steps. The first 2e(-) step forms the peroxide intermediate, followed by the second 2e(-) step to form the native intermediate, which has been shown to be the catalytically relevant fully oxidized form of the enzyme.
Topics: Binding Sites; Copper; Electron Transport; Kinetics; Laccase; Oxidation-Reduction; Oxygen; Quantum Theory
PubMed: 25572295
DOI: 10.1007/s00018-014-1826-6 -
Photochemistry and Photobiology May 2022Lipid hydroperoxides (LOOHs), including cholesterol- and phospholipid-derived species, are reactive intermediates that arise during photosensitized peroxidation of... (Review)
Review
Lipid hydroperoxides (LOOHs), including cholesterol- and phospholipid-derived species, are reactive intermediates that arise during photosensitized peroxidation of unsaturated lipids in biological membranes. These intermediates may appear in cancer cell membranes during anti-tumor photodynamic therapy (PDT). Photodynamically generated LOOHs have several different fates, including (a) iron-catalyzed one-electron reduction to free radical species which trigger damaging chain peroxidation reactions, (b) selenoperoxidase-catalyzed two-electron reduction to redox-inert alcohols (LOHs), and (c) spontaneous or protein-mediated translocation to other lipid membrane compartments where (a) or (b) may take place. These different LOOH fates will be described in this review, but with special attention to category (c), which the authors were the first to describe and characterize. Seminal early findings on cholesterol hydroperoxide (ChOOH) translocation and its potential negative consequences will be discussed. In reviewing this work, we wish to congratulate Jean Cadet, for his many outstanding accomplishments as a photobiologist and P&P editor.
Topics: Free Radicals; Lipid Peroxidation; Lipid Peroxides; Oxidation-Reduction; Phospholipids
PubMed: 34633674
DOI: 10.1111/php.13537 -
Current Opinion in Chemical Biology Aug 2017Modern lipidomics analysis paints a dynamic picture of membrane organizations, as changing and adapting lipid assemblies that play an active role in cellular function.... (Review)
Review
Modern lipidomics analysis paints a dynamic picture of membrane organizations, as changing and adapting lipid assemblies that play an active role in cellular function. This article highlights how the lipid composition of membranes determines specific organelle functions, how homeostatic mechanisms maintain these functions by regulating physical properties of membranes, and how cells disrupt lipid homeostasis to bring about regulated cell death (RCD). These are broad phenomena, and representative examples are reviewed here. In particular, the mechanisms of ferroptosis - a form of RCD brought about by lipid peroxidation - are highlighted, demonstrating how lipid metabolism drives cells' lipid composition toward states of increased sensitivity to lipid oxidation. An understanding of these interactions has begun to give rise to lipid-based therapies. This article reviews current successes of such therapies, and suggests directions for future developments.
Topics: Animals; Cell Death; Cell Membrane; Homeostasis; Lipid Metabolism; Oxidation-Reduction
PubMed: 28645028
DOI: 10.1016/j.cbpa.2017.06.002 -
Current Opinion in Pharmacology Apr 2017Aldehydes are continuously formed in biological systems through enzyme-dependent and spontaneous oxidation of lipids, glucose, and primary amines. These highly reactive,... (Review)
Review
Aldehydes are continuously formed in biological systems through enzyme-dependent and spontaneous oxidation of lipids, glucose, and primary amines. These highly reactive, biogenic electrophiles can become toxic via covalent modification of proteins, lipids and DNA. Thus, agents that scavenge aldehydes through conjugation have therapeutic value for a number of major cardiovascular diseases. Several commonly-prescribed drugs (e.g., hydralazine) have been shown to have potent aldehyde-conjugating properties which may contribute to their beneficial effects. Herein, we briefly describe the major sources and toxicities of biogenic aldehydes in cardiovascular system, and provide an overview of drugs that are known to have aldehyde-conjugating effects. Some compounds of phytochemical origin, and histidyl-dipeptides with emerging therapeutic value in this area are also discussed.
Topics: Aldehydes; Animals; Cardiovascular Diseases; Dipeptides; Humans; Oxidation-Reduction; Phytochemicals
PubMed: 28528297
DOI: 10.1016/j.coph.2017.04.004 -
Seminars in Cell & Developmental Biology Aug 2018As sessile oxygenic organisms with a plastic developmental programme, plants are uniquely positioned to exploit reactive oxygen species (ROS) as powerful signals. Plants... (Review)
Review
As sessile oxygenic organisms with a plastic developmental programme, plants are uniquely positioned to exploit reactive oxygen species (ROS) as powerful signals. Plants harbor numerous ROS-generating pathways, and these oxidants and related redox-active compounds have become tightly embedded into plant function and development during the course of evolution. One dominant view of ROS-removing systems sees them as beneficial antioxidants battling to keep damaging ROS below dangerous levels. However, it is now established that ROS are a necessary part of subcellular and intercellular communication in plants and that some of their signaling functions require ROS-metabolizing systems. For these reasons, it is suggested that "ROS processing systems" would be a more accurate term than "antioxidative systems" to describe cellular components that are most likely to interact with ROS and, in doing so, transmit oxidative signals. Within this framework, our update provides an overview of the complexity and compartmentation of ROS production and removal. We place particular emphasis on the importance of ROS-interacting systems such as the complex cellular thiol network in the redox regulation of phytohormone signaling pathways that are crucial for plant development and defense against external threats.
Topics: Animals; Antioxidants; Humans; Oxidation-Reduction; Oxidative Stress; Oxygen; Plant Physiological Phenomena; Reactive Oxygen Species
PubMed: 28733165
DOI: 10.1016/j.semcdb.2017.07.013 -
Oxidative Medicine and Cellular... 2019
Topics: Humans; Oxidation-Reduction; Signal Transduction
PubMed: 31191801
DOI: 10.1155/2019/6414975 -
Oxidative Medicine and Cellular... 2016
Topics: Animals; Antioxidants; Humans; Oxidation-Reduction; Oxidative Stress; Renal Insufficiency, Chronic
PubMed: 27579156
DOI: 10.1155/2016/8375186 -
Redox Biology May 2019Lipoproteins are essential systemic lipid transport particles, composed of apolipoproteins embedded in a phospholipid and cholesterol monolayer surrounding a cargo of... (Review)
Review
Lipoproteins are essential systemic lipid transport particles, composed of apolipoproteins embedded in a phospholipid and cholesterol monolayer surrounding a cargo of diverse lipid species. Many of the lipids present are susceptible to oxidative damage by lipid peroxidation, giving rise to the formation of reactive lipid peroxidation products (rLPPs). In view of the close proximity of the protein and lipid moieties within lipoproteins, the probability of adduct formation between rLPPs and amino acid residues of the proteins, a process called lipoxidation, is high. There has been interest for many years in the biological effects of such modifications, but the field has been limited to some extent by the availability of methods to determine the sites and exact nature of such modification. More recently, the availability of a wide range of antibodies to lipoxidation products, as well as advances in analytical techniques such as liquid chromatography tandem mass spectrometry (LC-MSMS), have increased our knowledge substantially. While most work has focused on LDL, oxidation of which has long been associated with pro-inflammatory responses and atherosclerosis, some studies on HDL, VLDL and Lipoprotein(a) have also been reported. As the broader topic of LDL oxidation has been reviewed previously, this review focuses on lipoxidative modifications of lipoproteins, from the historical background through to recent advances in the field. We consider the main methods of analysis for detecting rLPP adducts on apolipoproteins, including their advantages and disadvantages, as well as the biological effects of lipoxidized lipoproteins and their potential roles in diseases.
Topics: Animals; Biological Assay; Biomarkers; Drug Discovery; Humans; Lipid Metabolism; Lipid Peroxidation; Lipids; Lipoproteins; Mass Spectrometry; Oxidation-Reduction; Structure-Activity Relationship
PubMed: 30579928
DOI: 10.1016/j.redox.2018.101066