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587 result(s) for "Singlet Oxygen - metabolism"
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Singlet Oxygen-Induced Cell Death in Arabidopsis under High-Light Stress Is Controlled by OXI1 Kinase
Studies of the singlet oxygen (¹O₂)-overproducing flu and chlorina1 (ch1) mutants of Arabidopsis (Arabidopsis thaliana) have shown that ¹O₂-induced changes in gene expression can lead to either programmed cell death (PCD) or acclimation. A transcriptomic analysis of the ch1 mutant has allowed the identification of genes whose expression is specifically affected by each phenomenon. One such gene is OXIDATIVE SIGNAL INDUCIBLE1 (OXI1) encoding an AGC kinase that was noticeably induced by excess light energy and ¹O₂ stress conditions leading to cell death. Photo-induced oxidative damage and cell death were drastically reduced in the OXI1 null mutant (oxi1) and in the double mutant ch1*oxi1 compared with the wild type and the ch1 single mutant, respectively. This occurred without any changes in the production rate of ¹O₂ but was cancelled by exogenous applications of the phytohormone jasmonate. OXI1-mediated ¹O₂ signaling appeared to operate through a different pathway from the previously characterized OXI1-dependent response to pathogens and H₂O₂ and was found to be independent of the EXECUTER proteins. In high-light-stressed plants, the oxi1 mutation was associated with reduced jasmonate levels and with the up-regulation of genes encoding negative regulators of jasmonate signaling and PCD. Our results show that OXI1 is a new regulator of ¹O₂-induced PCD, likely acting upstream of jasmonate.
Superoxide and Singlet Oxygen Produced within the Thylakoid Membranes Both Cause Photosystem I Photoinhibition
Photosystem I (PSI) photoinhibition suppresses plant photosynthesis and growth. However, the mechanism underlying PSI photoinhibition has not been fully clarified. In this study, in order to investigate the mechanism of PSI photoinhibition in higher plants, we applied repetitive short-pulse (rSP) illumination, which causes PSI-specific photoinhibition in chloroplasts isolated from spinach leaves. We found that rSP treatment caused PSI photoinhibition, but not PSII photoinhibition in isolated chloroplasts in the presence of O₂. However, chloroplastic superoxide dismutase and ascorbate peroxidase activities failed to protect PSI from its photoinhibition. Importantly, PSI photoinhibition was largely alleviated in the presence of methyl viologen, which stimulates the production of reactive oxygen species (ROS) at the stromal region by accepting electrons from PSI, even under the conditions where CuZn-superoxide dismutase and ascorbate peroxidase activities were inactivated by KCN. These results suggest that the ROS production site, but not the ROS production rate, is critical for PSI photoinhibition. Furthermore, we found that not only superoxide (O₂⁻) but also singlet oxygen (¹O₂) is involved in PSI photoinhibition induced by rSP treatment. From these results, we suggest that PSI photoinhibition is caused by both O₂⁻ and ¹O2 produced within the thylakoid membranes when electron carriers in PSI become highly reduced. Here, we show, to our knowledge, new insight into the PSI photoinhibition in higher plants.
Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy
Photodynamic therapy (PDT) kills cancer cells by converting tumour oxygen into reactive singlet oxygen ( 1 O 2 ) using a photosensitizer. However, pre-existing hypoxia in tumours and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers photodynamic efficacy. Here to overcome this problem, we create oxygen self-enriching photodynamic therapy (Oxy-PDT) by loading a photosensitizer into perfluorocarbon nanodroplets. Because of the higher oxygen capacity and longer 1 O 2 lifetime of perfluorocarbon, the photodynamic effect of the loaded photosensitizer is significantly enhanced, as demonstrated by the accelerated generation of 1 O 2 and elevated cytotoxicity. Following direct injection into tumours, in vivo studies reveal tumour growth inhibition in the Oxy-PDT-treated mice. In addition, a single-dose intravenous injection of Oxy-PDT into tumour-bearing mice significantly inhibits tumour growth, whereas traditional PDT has no effect. Oxy-PDT may enable the enhancement of existing clinical PDT and future PDT design. Photodynamic therapy is used in cancer treatment and generates reactive oxygen species to kill tumour cells but is limited by the availability of oxygen. Here, the authors modify a photodynamic sensitiser so that it produces excess oxygen species and show enhanced tumour cell killing in vitro and in vivo .
Significance of Singlet Oxygen Molecule in Pathologies
Reactive oxygen species, including singlet oxygen, play an important role in the onset and progression of disease, as well as in aging. Singlet oxygen can be formed non-enzymatically by chemical, photochemical, and electron transfer reactions, or as a byproduct of endogenous enzymatic reactions in phagocytosis during inflammation. The imbalance of antioxidant enzymes and antioxidant networks with the generation of singlet oxygen increases oxidative stress, resulting in the undesirable oxidation and modification of biomolecules, such as proteins, DNA, and lipids. This review describes the molecular mechanisms of singlet oxygen production in vivo and methods for the evaluation of damage induced by singlet oxygen. The involvement of singlet oxygen in the pathogenesis of skin and eye diseases is also discussed from the biomolecular perspective. We also present our findings on lipid oxidation products derived from singlet oxygen-mediated oxidation in glaucoma, early diabetes patients, and a mouse model of bronchial asthma. Even in these diseases, oxidation products due to singlet oxygen have not been measured clinically. This review discusses their potential as biomarkers for diagnosis. Recent developments in singlet oxygen scavengers such as carotenoids, which can be utilized to prevent the onset and progression of disease, are also described.
Heterometallic Ru–Pt metallacycle for two-photon photodynamic therapy
As an effective and noninvasive treatment of various diseases, photodynamic therapy (PTD) relies on the combination of light, a photosensitizer, and oxygen to generate cytotoxic reactive oxygen species that can damage malignant tissue. Much attention has been paid to covalent modifications of the photosensitizers to improve their photophysical properties and to optimize the pathway of the photosensitizers interacting with cells within the target tissue. Herein we report the design and synthesis of a supramolecular heterometallic Ru–Pt metallacycle via coordination-driven self-assembly. While inheriting the excellent photostability and two-photon absorption characteristics of the Ru(II) polypyridyl precursor, the metallacycle also exhibits red-shifted luminescence to the near-infrared region, a larger two-photon absorption cross-section, and higher singlet oxygen generation efficiency, making it an excellent candidate as a photosensitizer for PTD. Cellular studies reveal that the metallacycle selectively accumulates in mitochondria and nuclei upon internalization. As a result, singlet oxygen generated by photoexcitation of the metallacycle can efficiently trigger cell death via the simultaneous damage to mitochondrial function and intranuclear DNA. In vivo studies on tumor-bearing mice show that the metallacycle can efficiently inhibit tumor growth under a low light dose with minimal side effects. The supramolecular approach presented in this work provides a paradigm for the development of PDT agents with high efficacy.
Nano-photosensitizer based on layered double hydroxide and isophthalic acid for singlet oxygenation and photodynamic therapy
Singlet oxygen has won a great deal of attention to catalysis and biological studies due to its strong oxidizing properties. However, the photosensitizers which require for the generation of singlet oxygen remain inadequate because of their lack of long-wavelength absorption, weak hydrophilicity, and poor biocompatibility. Here, we develop near-infrared laser activated supramolecular photosensitizers (isophthalic acid/layered double hydroxide nanohybrids) for efficient two-photon photodynamic therapy. The singlet oxygen quantum yield of nanohybrid is up to 0.74. Critically, in vitro tests verify the superior anti-cancer properties of nanohybrid with an IC 50 determine to be 0.153 μg mL −1 . The nanohybrids take advantage of the superior tissue penetration of 808 nm laser irradiation and exhibit a dramatically strong ability to ablate tumors in vivo, with extremely low toxicity. This work provides the proof of concept that ultralong-lived triplet excitons can function as two-photon-activated photosensitizers for an effective singlet oxygen generation. Usually, several components are needed for efficient 2-photon photodynamic therapy (PDT). Here, the authors sandwiched carboxylic acids between layered double hydroxide nanosheets to obtain a single-handed biocompatible photosensitizer that generates singlet oxygen in high quantum yield.
A bacterial light response reveals an orphan desaturase for human plasmalogen synthesis
Plasmalogens are glycerophospholipids with a hallmark sn-1 vinyl ether bond. These lipids are found in animals and some bacteria and have proposed membrane organization, signaling, and antioxidant roles. We discovered the plasmanylethanolamine desaturase activity that is essential for vinyl ether bond formation in a bacterial enzyme, CarF, which is a homolog of the human enzyme TMEM189. CarF mediates light-induced carotenogenesis in Myxococcus xanthus, and plasmalogens participate in sensing photooxidative stress through singlet oxygen. TMEM189 and other animal homologs could functionally replace CarF in M. xanthus, and knockout of TMEM189 in a human cell line eliminated plasmalogens. Discovery of the human plasmanylethanolamine desaturase will spur further study of plasmalogen biogenesis, functions, and roles in disease.
Carotenoid oxidation products are stress signals that mediate gene responses to singlet oxygen in plants
1O2 (singlet oxygen) is a reactive O2 species produced from triplet excited chlorophylls in the chloroplasts, especially when plants are exposed to excess light energy. Similarly to other active O2 species, 1O2 has a dual effect: It is toxic, causing oxidation of biomolecules, and it can act as a signal molecule that leads to cell death or to acclimation. Carotenoids are considered to be the main 1O2 quenchers in chloroplasts, and we show here that light stress induces the oxidation of the carotenoid β-carotene in Arabidopsis plants, leading to the accumulation of different volatile derivatives. One such compound, β-cyclocitral, was found to induce changes in the expression of a large set of genes that have been identified as 1O2 responsive genes. In contrast, β-cyclocitral had little effect on the expression of H2O2 gene markers. β-Cyclocitral–induced reprogramming of gene expression was associated with an increased tolerance to photooxidative stress. The results indicate that β-cyclocitral is a stress signal produced in high light that is able to induce defense mechanisms and represents a likely messenger involved in the 1O2 signaling pathway in plants.
Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy
As the first line of innate immune cells to migrate towards tumour tissue, neutrophils, can immediately kill abnormal cells and activate long-term specific adaptive immune responses. Therefore, the enzymes mediated elevation of reactive oxygen species (ROS) bioinspired by neutrophils can be a promising strategy in cancer immunotherapy. Here, we design a core-shell supramolecular hybrid nanogel via the surface phosphatase triggered self-assembly of oligopeptides around iron oxide nanoparticles to simulate productive neutrophil lysosomes. The cascade reaction of superoxide dismutase (SOD) and chloroperoxidase (CPO) within the bioinspired nanogel can convert ROS in tumour tissue to hypochlorous acid (HOCl) and the subsequent singlet oxygen ( 1 O 2 ) species. Studies on both cells and animals demonstrate successful 1 O 2 -mediated cell/tumour proliferation inhibition, making this enzyme therapy capable for treating tumours without external energy activation. Enzymatic reactions caused by neutrophils can cause the elevation of reactive oxygen species (ROS) in tumour tissue, Here, the authors, inspired by the neutrophils, design and test a synthetic cascade reaction which turns ROS into singlet oxygen and demonstrate the application of the designed nanoparticle
Recent advances in innovative strategies for enhanced cancer photodynamic therapy
Photodynamic therapy (PDT), a non-invasive therapeutic modality, has received increasing attention owing to its high selectivity and limited side effects. Although significant clinical research progress has been made in PDT, the breadth and depth of its clinical application have not been fully realized due to the limitations such as inadequate light penetration depth, non-targeting photosensitizers (PSs), and tumor hypoxia. Consequently, numerous investigations put their emphasis on innovative strategies to overcome the aforementioned limitations and enhance the therapeutic effect of PDT. Herein, up-to-date advances in these innovative methods for PDT are summarized by introducing the design of PS systems, their working mechanisms and application examples. In addition, current challenges of these innovative strategies for clinical application, and future perspectives on further improvement of PDT are also discussed.