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DOE OSTI2025

Oxidative stress is a shared characteristic of ME/CFS and Long COVID

Over 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition marked by fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). With no clinically approved treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in 25 healthy controls, 27 ME/CFS, and 20 LC donors, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, especially in the memory subset. Using a combination of flow cytometry, RNA-seq, mass spectrometry, and systems chemistry analysis, we observed aberrations in reactive oxygen species (ROS) clearance pathways including elevated glutathione levels, decreases in mitochondrial superoxide dismutase protein levels, and glutathione peroxidase 4–mediated lipid oxidative damage. Strikingly, these redox pathways changes show sex-specific trends. While ME/CFS females exhibit higher total ROS and mitochondrial calcium levels, males have normal ROS levels, with pronounced mitochondrial lipid oxidative damage. In females, these higher ROS levels correlate with T cell hyperproliferation, consistent with the known role of elevated ROS in initiating proliferation. This hyperproliferation can be attenuated by metformin, suggesting this Food and Drug Administration (FDA)-approved drug as a possible treatment, as also suggested by a recent clinical study of LC patients. Moreover, these results suggest a shared mechanistic basis for the systemic phenotypes of ME/CFS and LC, which can be detected by quantitative blood cell measurements, and that effective, patient-tailored drugs might be discovered using standard lymphocyte stimulation assays.

ME/CFS↗

DOE OSTI2022

A Double-Pronged Sword: XJB-5-131 Is a Suppressor of Somatic Instability and Toxicity in Huntington’s Disease

Due to large increases in the elderly populations across the world, age-related diseases are expected to expand dramatically in the coming years. Among these, neurodegenerative diseases will be among the most devastating in terms of their emotional and economic impact on patients, their families, and associated subsidized health costs. There is no currently available cure or rescue for dying brain cells. Viable therapeutics for any of these disorders would be a breakthrough and provide relief for the large number of affected patients and their families. Neurodegeneration is accompanied by elevated oxidative damage and inflammation. While natural antioxidants have largely failed in clinical trials, preclinical phenotyping of the unnatural, mitochondrial targeted nitroxide, XJB-5-131, bodes well for further translational development in advanced animal models or in humans. Here we consider the usefulness of synthetic antioxidants for the treatment of Huntington’s disease. The mitochondrial targeting properties of XJB-5-131 have great promise. It is both an electron scavenger and an antioxidant, reducing both somatic expansion and toxicity simultaneously through the same redox mechanism. By quenching reactive oxygen species, XJB-5-131 breaks the cycle between the rise in oxidative damage during disease progression and the somatic growth of the CAG repeat which depends on oxidation.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Enhanced Salt Tolerance of Torreya grandis Genders Is Related to Nitric Oxide Level and Antioxidant Capacity

Nitric oxide (NO), a bioactive molecule, is often involved in the regulation of physiological and biochemical processes in stressed plants. However, the effects of NO donors on dioecious plants remain unclear. Using a pot experiment, female and male Torreya grandis were used to study the role of sex and NO in salt stress tolerance. In the present study, female and male T. grandis seedlings pretreated with an NO donor (sodium nitroprusside, SNP) were exposed to salt stress, and then leaf relative water content (RWC), photosynthetic pigments, chlorophyll fluorescence parameters, NO and glutathione levels, oxidative damage, and antioxidant enzyme activities were investigated. Female T. grandis plants had better tolerance to salinity, as they were characterized by significantly higher RWC, pigment content, and photochemical activities of photosystem II (PSII) and fewer negative effects associated with higher nitrate reductase (NR) activity and NO content. Pretreatment with an NO donor further increased the endogenous NO content and NR activity of both female and male T. grandis plants compared with salt treatment. Moreover, pretreatment with an NO donor alleviated salt-induced oxidative damage of T. grandis , especially in male plants, as indicated by reduced lipid peroxidation, through an enhanced antioxidant system, including proline and glutathione accumulation, and increased antioxidant enzyme activities. However, the ameliorating effect of the NO donor was not effective in the presence of the NO scavenger (Nω-nitro-L-arginine methyl ester, L-name). In conclusion, enhanced salt tolerance in T. grandis plants is related to nitric oxide levels and the supply of NO donors is an interesting strategy for alleviating the negative effect of salt on T. grandis . Our data provide new evidence to contribute to the current understanding of NO-induced salt stress tolerance.

Liu, Yang↗

DOE OSTI2024

Bacterial Volatile Organic Compounds as a Strategy to Increase Drought Tolerance in Maize (Zea mays L.): Influence on Plant Biochemistry

Maize is highly susceptible to drought, which affects growth and yield. This study investigated how bacterial volatile organic compounds (BVOCs) affect maize drought tolerance. Drought reduced shoot size but increased root length, an adaptation for accessing deeper soil moisture. BVOCs from strain D12 significantly increased root length and shoot growth under drought conditions. Drought also altered root biochemistry, decreasing enzyme activity, and increased osmolyte levels. BVOCs from strains F11 and FS4-14 further increased osmolyte levels but did not protect membranes from oxidative damage, while BVOCs from strains D12 and D7 strains reduced osmolyte levels and cell damage. In shoots, drought increased the levels of osmolytes and oxidative stress markers. BVOCs from FS4-14 had minimal effects on shoot biochemistry. BVOCs from D12 and F11 partially restored metabolic activity but did not reduce cell damage. BVOCs from D7 reduced metabolic activity and cell damage. These results suggest that BVOCs can modulate the biochemical response of maize to drought, with some strains evidencing the potential to enhance drought tolerance.

Lopes, Tiago (ORCID:0000000330603315)↗

DOE OSTI2021

Singlet Oxygen Leads to Structural Changes to Chloroplasts during their Degradation in the Arabidopsis thaliana plastid ferrochelatase two Mutant

Abstract During stress, chloroplasts produce large amounts of reactive oxygen species (ROS). Chloroplasts also contain many nutrients, including 80% of a leaf’s nitrogen supply. Therefore, to protect cells from photo-oxidative damage and to redistribute nutrients to sink tissues, chloroplasts are prime targets for degradation. Multiple chloroplast degradation pathways are induced by photo-oxidative stress or nutrient starvation, but the mechanisms by which damaged or senescing chloroplasts are identified, transported to the central vacuole and degraded are poorly defined. Here, we investigated the structures involved with degrading chloroplasts induced by the ROS singlet oxygen (1O2) in the Arabidopsis thaliana plastid ferrochelatase two (fc2) mutant. Under mild 1O2 stress, most fc2 chloroplasts appeared normal, but had reduced starch content. A subset of chloroplasts was degrading, and some protruded into the central vacuole via ‘blebbing’ structures. A 3D electron microscopy analysis demonstrated that up to 35% of degrading chloroplasts contained such structures. While the location of a chloroplast within a cell did not affect the likelihood of its degradation, chloroplasts in spongy mesophyll cells were degraded at a higher rate than those in palisade mesophyll cells. To determine if degrading chloroplasts have unique structural characteristics, allowing them to be distinguished from healthy chloroplasts, we analyzed fc2 seedlings grown under different levels of photo-oxidative stress. A correlation was observed among chloroplast swelling, 1O2 signaling and the state of degradation. Finally, plastoglobule (PG) enzymes involved in chloroplast disassembly were upregulated while PGs increased their association with the thylakoid grana, implicating an interaction between 1O2-induced chloroplast degradation and senescence pathways.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Structural and biochemical insights into NEIL2’s preference for abasic sites

Cellular DNA is subject to damage from a multitude of sources and repair or bypass of sites of damage utilize an array of context or cell cycle dependent systems. The recognition and removal of oxidatively damaged bases is the task of DNA glycosylases from the base excision repair pathway utilizing two structural families that excise base lesions in a wide range of DNA contexts including duplex, single-stranded and bubble structures arising during transcription. The mammalian NEIL2 glycosylase of the Fpg/Nei family excises lesions from each of these DNA contexts favoring the latter two with a preference for oxidized cytosine products and abasic sites. We have determined the first liganded crystal structure of mammalian NEIL2 in complex with an abasic site analog containing DNA duplex at 2.08 Å resolution. Comparison to the unliganded structure revealed a large interdomain conformational shift upon binding the DNA substrate accompanied by local conformational changes in the C-terminal domain zinc finger and N-terminal domain void-filling loop necessary to position the enzyme on the DNA. The detailed biochemical analysis of NEIL2 with an array of oxidized base lesions indicates a significant preference for its lyase activity likely to be paramount when interpreting the biological consequences of variants.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2020

Photodamage and Repair in Higher Plant Photosynthesis (Final Technical Report)

Elucidation of the functional properties and structural organization of membrane protein complexes is one of the central objectives of current biochemical investigation. One of the most intriguing aspects of membrane protein function is its role in the mediation of energy transduction in photosynthetic organisms. Light energy, which is the product of a most violent physical process, fusion, is transformed into biological energy equivalents utilized by the photosynthetic cell. This photosynthetic process provides both the carbohydrate that lies at the base of virtually all food chains and, as a byproduct, all of the atmospheric oxygen utilized by heterotrophic organisms. The photosynthetic apparatus, however, is quite susceptible to damage by Reactive Oxygen Species (ROS). These species include O2 ·– , ·OH, H 2 O 2 and 1 O 2 . The production of ROS is an unavoidable byproduct of electron transport under aerobic conditions and these can damage lipids, nucleic acids and proteins. Our research has centered on the identification of amino acid oxidative damage which occurs in the vicinity of photosynthetic energy transfer cofactors. These cofactors participate in excitation energy transfer and linear electron transport within Photosystem II, the Cytochrome b 6 ƒ complex and Photosystem I. Additionally, we have participated in a number of productive collaborations leveraging our expertise in photosynthetic measurements and mass spectrometry to assist other investigators in their research.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Distonic radical anion species in cysteine oxidation processes

Oxidation of cysteine residues constitutes an important regulatory mechanism in the function of biological systems. Much of this behavior is controlled by the specific chemical properties of the thiol side-chain group, where reac-tions with reactive oxygen species take place. Herein, we in-vestigated the entire cysteine oxidation cycle Cys-SH ? Cys-SOnH (n = 1, 2, 3) using cryogenic negative ion photoelectron spectroscopy and quantum-chemical calculations. The conven-tional view on the first reversible oxidation step (n = 1) is as-sociated with sulfinate species. Yet our results indicate that an alternative option exists in the form of novel distonic radical anion •OS-CH2CH(NH2)-COO- with an unpaired electron on the thiol group and excess negative charge on the carboxylate. Higher order oxidation states (n = 2, 3) are thought to be asso-ciated with irreversible oxidative damage, and our results show that excess negative charge in those cases migrates to -SOn- group. Furthermore, these species are stable towards 1e oxidation, as opposed to the n = 1 case that undergoes intra-molecular proton transfer. The molecular level insights report-ed in this work provide direct spectroscopic evidences towards unique chemical versatility of Cys-sulfenic acid (Cys-SOH) in post-translational modifications of protein systems. This research was supported by the U.S. Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences (X.-B. W. and M. V.) and was performed at the EMSL, a national scientific user facility sponsored by DOE's Office of Biological and Environmental Research and located at the Pacific Northwest National Laboratory. Z. B. Q. acknowledges additional support from the National Natural Science Foundation of China (Grant No. 21873003 and 21503003) and the Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the second phase) (Grant No. U1501501) and Super Computation of Shenzhen.

Qin, Zhengbo↗

DOE OSTI2021

The core autophagy machinery is not required for chloroplast singlet oxygen-mediated cell death in the Arabidopsis thaliana plastid ferrochelatase two mutant

Chloroplasts respond to stress and changes in the environment by producing reactive oxygen species (ROS) that have specific signaling abilities. The ROS singlet oxygen ( 1 O 2 ) is unique in that it can signal to initiate cellular degradation including the selective degradation of damaged chloroplasts. This chloroplast quality control pathway can be monitored in the Arabidopsis thaliana mutant plastid ferrochelatase two ( fc2 ) that conditionally accumulates chloroplast 1 O 2 under diurnal light cycling conditions leading to rapid chloroplast degradation and eventual cell death. The cellular machinery involved in such degradation, however, remains unknown. Recently, it was demonstrated that whole damaged chloroplasts can be transported to the central vacuole via a process requiring autophagosomes and core components of the autophagy machinery. The relationship between this process, referred to as chlorophagy, and the degradation of 1 O 2 -stressed chloroplasts and cells has remained unexplored. Results To further understand 1 O 2 -induced cellular degradation and determine what role autophagy may play, the expression of autophagy-related genes was monitored in 1 O 2 -stressed fc2 seedlings and found to be induced. Although autophagosomes were present in fc2 cells, they did not associate with chloroplasts during 1 O 2 stress. Mutations affecting the core autophagy machinery ( atg5 , atg7 , and atg10 ) were unable to suppress 1 O 2 -induced cell death or chloroplast protrusion into the central vacuole, suggesting autophagosome formation is dispensable for such 1 O 2 –mediated cellular degradation. However, both atg5 and atg7 led to specific defects in chloroplast ultrastructure and photosynthetic efficiencies, suggesting core autophagy machinery is involved in protecting chloroplasts from photo-oxidative damage. Finally, genes predicted to be involved in microautophagy were shown to be induced in stressed fc2 seedlings, indicating a possible role for an alternate form of autophagy in the dismantling of 1 O 2 -damaged chloroplasts. Conclusions Our results support the hypothesis that 1 O 2 -dependent cell death is independent from autophagosome formation, canonical autophagy, and chlorophagy. Furthermore, autophagosome-independent microautophagy may be involved in degrading 1 O 2 -damaged chloroplasts. At the same time, canonical autophagy may still play a role in protecting chloroplasts from 1 O 2 -induced photo-oxidative stress. Together, this suggests chloroplast function and degradation is a complex process utilizing multiple autophagy and degradation machineries, possibly depending on the type of stress or damage incurred.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Metabolic versatility of the nitrite-oxidizing bacterium Nitrospira marina and its proteomic response to oxygen-limited conditions

The genus Nitrospira is the most widespread group of nitrite-oxidizing bacteria and thrives in diverse natural and engineered ecosystems. Nitrospira marina Nb-295 T was isolated from the ocean over 30 years ago; however, its genome has not yet been analyzed. Here, we investigated the metabolic potential of N. marina based on its complete genome sequence and performed physiological experiments to test genome-derived hypotheses. Our data confirm that N. marina benefits from additions of undefined organic carbon substrates, has adaptations to resist oxidative, osmotic, and UV light-induced stress and low dissolved p CO 2 , and requires exogenous vitamin B 12 . In addition, N. marina is able to grow chemoorganotrophically on formate, and is thus not an obligate chemolithoautotroph. We further investigated the proteomic response of N. marina to low (~5.6 µM) O 2 concentrations. The abundance of a potentially more efficient CO 2 -fixing pyruvate:ferredoxin oxidoreductase (POR) complex and a high-affinity cbb 3 -type terminal oxidase increased under O 2 limitation, suggesting a role in sustaining nitrite oxidation-driven autotrophy. This putatively more O 2 -sensitive POR complex might be protected from oxidative damage by Cu/Zn-binding superoxide dismutase, which also increased in abundance under low O 2 conditions. Furthermore, the upregulation of proteins involved in alternative energy metabolisms, including Group 3b [NiFe] hydrogenase and formate dehydrogenase, indicate a high metabolic versatility to survive conditions unfavorable for aerobic nitrite oxidation. In summary, the genome and proteome of the first marine Nitrospira isolate identifies adaptations to life in the oxic ocean and provides insights into the metabolic diversity and niche differentiation of NOB in marine environments.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

A Multiphysics Multiscale Simulation Platform for Damage, Environmental Degradation, and Life Prediction of CMCs in Extreme Environments

This project successfully developed a multiphysics, multiscale computational framework to enhance the design and development of CMCs, with a focus on modeling highly nonlinear, time-dependent damage mechanisms and material degradation under extreme conditions, such as those experienced in turbine service environments. The project made significant advances in improving our understanding of progressive damage, oxidative degradation, and time-dependent inelastic deformation in CMCs, with particular attention to the role of uncertainties in predictions. Key outcomes include the integration of advanced material characterization, uncertainty quantification, and multiphysics constitutive models to predict the behavior of CMCs over their service life. A novel multiscale methodology was employed, which integrated microscale constituent behaviors with structural-scale responses, enabling the manufacturing defects in the microstructure that are prone to damage nucleation. Through the development of DL algorithms, the project advanced the prediction of damage initiation and crack propagation, taking into account the defect morphology and statistical variations across multiple scales. The framework was rigorously validated using thermomechanical experiments, which tested CMCs under various mechanical loadings at elevated temperatures, further enhancing the model's predictive capability. Overall, the research outcomes have provided a more accurate, reliable method for predicting CMC component life, significantly advancing material design, and improving component reliability in extreme environments. This work has strong implications for the optimization of turbine components and other high-performance applications where CMCs are used.

03 NATURAL GAS↗

DOE OSTI2020

Skeletal tissue regulation by catalase overexpression in mitochondria

Accumulation of oxidative damage from excess reactive oxygen species (ROS) may contribute to skeletal aging and mediate adverse responses to physiological challenges. Wild-type (WT) mice and transgenic mice (male, 16 wk of age) with human catalase targeted to the mitochondria (mCAT) were analyzed for skeletal responses to the remodeling stimuli of combined hind-limb unloading and exposure to ionizing radiation ( 137 Cs, 2 Gy). Treatment for 2 wk caused lipid peroxidation in the bones WT but not mCAT mice, showing that transgene expression mitigated oxidative stress. Ex vivo osteoblast colony growth rate was 95% greater in mCAT than WT mice and correlated with catalase activity levels ( P < 0.005, r = 0.67), although terminal osteoblast and osteoclast differentiation were unaffected. mCAT mice had lower cancellous bone volume and cortical size than WT mice. Ambulatory control mCAT animals also displayed reduced cancellous and cortical structural properties compared with control WT mice. In mCAT but not WT mice, treatment caused an unexpectedly rapid radial expansion (+8% cortical area, +22% moment of inertia), reminiscent of compensatory bone growth during advancing age. In contrast, treatment caused similar structural deficits in cancellous tissue of mCAT and WT mice. In sum, mitochondrial ROS signaling via H 2 O 2 was important for the acquisition of adult bone structure and catalase overexpression failed to protect cancellous tissue from treatment. In contrast, catabolic stimuli caused radial expansion in mCAT not WT mice, suggesting that mitochondrial ROS in skeletal cells act to suppress tissue turnover in response to remodeling challenges.

Cell Biology↗

DOE OSTI2023

SAM Code Development for Source Term Modeling in Fluoride-salt-cooled High-temperature Reactors

The SAM code is under development and supported by DOE-NE’s Nuclear Energy Advanced Modeling and Simulation program as a modern system-level modeling and simulation tool for advanced non-light water reactor safety analyses. These advanced reactor concepts incorporate novel and improved approaches to achieve safety and economic feasibility. Many concepts leverage higher operating temperatures for improved efficiency with a variety of coolants and structural materials to support those needs. Such design choices may also pose unique radiological source term risks. There are continuous efforts to incorporate new physics and phenomena relevant to advanced reactor concepts, including capabilities to enable system-level source term modeling. The Pebble-Bed Fluoride-salt-cooled High-temperature Reactor (PB-FHR) is a promising candidate among advanced nuclear reactor concepts with its improved passive safety characteristics and high thermal efficiency. In addition to past efforts to support the development and utilization of SAM for PB-FHR safety analysis, the species transport modeling capabilities in SAM have been extended to simulate source term phenomena in concepts like the PB-FHR. The PB-FHR concept utilizes pebble-form TRISO fuel and FLiBe salt coolant to provide robust barriers to the release of almost all fission products and radiological source terms. However, tritium poses a unique radiological risk due to its significant production from neutron interactions with 6 Li and 9 Be in the FLiBe as well as its high mobility at elevated temperatures where it can permeate through structural metals. Secondly, the use of graphite at elevated temperatures poses the risk of oxidation damage to any structural components or fuel pebbles that are exposed to accidental air ingress. This report summarizes progress made in modeling these phenomena in SAM, which leverages the system-level multi-physics thermal hydraulic simulation to support an effective engineering-scale source term modeling capability. A tritium transport model is developed to simulate the various transport pathways in FHR and MSR concepts and is presented through verification and validation examples as well as demonstrations simulating experimental test loops and reference plant FHR models. A graphite oxidation model is also introduced to calculate local oxidation rates and is presented with initial validation results.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

DOE OSTI2021

Abscisic Acid Mediates Grafting-Induced Cold Tolerance of Watermelon via Interaction With Melatonin and Methyl Jasmonate

Grafting is widely used to increase plant defense responses to various stresses. Grafting-induced cold tolerance is associated with the increase of the antioxidant potential of plants; however, the underlying mechanisms remain unclear. Here, we found that pumpkin rootstocks promote antioxidant enzyme activities and alleviate cold-induced oxidative damage, accompanied by increased abscisic acid (ABA), melatonin, and methyl jasmonate (MeJA) levels in leaves. Increased ABA accumulation in leaves was attributed partly to the increased ABA levels in rootstocks. ABA induced antioxidant enzymes activities and the accumulation of melatonin and MeJA, while inhibition of ABA synthesis blocked the rootstock-induced antioxidant activity and the accumulation of melatonin and MeJA under cold stress. Melatonin and MeJA application also enhanced ABA accumulation in leaves after cold exposure, whereas inhibition of melatonin or MeJA synthesis attenuated the rootstock-induced increase of ABA. Moreover, melatonin and MeJA application alleviated cold-induced oxidative stress, but inhibition of melatonin or MeJA synthesis lowered the rootstock- or ABA-induced antioxidant potential and tolerance to cold. These findings indicate that ABA plays an important role in the grafting-induced cold tolerance by promoting the accumulation of melatonin and MeJA, which in turn, promote ABA accumulation, forming a positive feedback loop.

Guo, Yanliang↗

DOE OSTI2023

Electronic Excitation Response of DNA to High-Energy Proton Radiation in Water

The lack of molecular-level understanding for the electronic excitation response of DNA to charged particle radiation, such as high-energy protons, remains a fundamental scientific bottleneck in advancing proton and other ion beam cancer therapies. In particular, the dependence of different types of DNA damage on high-energy protons represents a significant knowledge void. Here, in this work, we employ first-principles real-time time-dependent density functional theory simulation, using a massively parallel supercomputer, to unravel the quantum-mechanical details of the energy transfer from high-energy protons to DNA in water. The calculations reveal that protons deposit significantly more energy onto the DNA sugar-phosphate side chains than onto the nucleobases, and greater energy transfer is expected onto the DNA side chains than onto water. As a result of this electronic stopping process, highly energetic holes are generated on the DNA side chains as a source of oxidative damage.

74 ATOMIC AND MOLECULAR PHYSICS↗

DOE OSTI2026

Characterization of Oxidative Modifications to Short Peptides Using Low Dose Rate X-Rays

The method of X-ray footprinting and mass spectrometry (XFMS) using high flux synchrotron X-ray sources has become an established method in structural biology and is based on the radiolytic production of hydroxyl radicals, which oxidatively modify protein sidechains. While other methods of producing hydroxyl radicals are available, one benefit of using high flux density sources is that hydroxyl radical scavenging reactions can be minimized, and exposure times kept short to minimize secondary reactions. Here we present an application of the XFMS method using low dose rate X-rays from a commercial instrument. We demonstrate the feasibility of the approach using short peptides, characterizing the oxidative modifications +14, +16, and +32 Da under both aerobic and low oxygen conditions, and we additionally quantify the hydrogen peroxide production for various doses using the low dose rate source. These results provide fundamental information on the oxidative damage to peptides due to hydroxyl radicals using a low dose rate X-ray source.

X-ray methods↗

DOE OSTI2022

Biochemical responses of hairgrass (Deschampsia caespitosa) to hydrological change

Plant growth and development are closely related to water availability. Water deficit and water excess are detrimental to plants, causing a series of damage to plant morphology, physiological and biochemical processes. In the long evolutionary process, plants have evolved an array of complex mechanisms to combat against stressful conditions. In the present study, the duration-dependent changes in ascorbate (AsA) and glutathione (GSH) contents and activities of enzymes involved in the AsA-GSH cycle in hairgrass ( Deschampsia caespitosa ) in response to water stress was investigated in a pot trial using a complete random block design. The treatments were as follows: (1) heavily waterlogging, (2) moderate waterlogging, (3) light waterlogging, (4) light drought, (5) moderate drought, (6) heavily drought, and (7) a control (CK) with plant be maintained at optimum water availability. The hairgrass plants were subjected to waterlogging or drought for 7, 14, 21 and 28 days and data were measured following treatment. Results revealed that hairgrass subjected to water stress can stimulate enzymatic activities of ascorbate peroxidase (APX), glutathione peroxidase (GPX), glutathione reductase (GR), dehydroascorbate reductase (DHAR), monodehydroascorbate reductase (MDHAR) and L-galactono-1, 4-lactone dehydrogenase (GalLDH), switched on the ascorbate-glutathione (AsA-GSH) cycle and the L-galactose synthesis, up-regulated the contents of AsA and GSH, and maintained higher ratios of ascorbate to dehydroascorbate (AsA/DHA) and reduced glutathione to oxidized glutathione (GSH/GSSG) to alleviate potential oxidative damage. However, the light waterlogging did not induce hairgrass under stress to switch on the AsA-GSH pathway. In general, the critic substances and enzyme activities in AsA-GSH metabolic pathway increased as the increase of water stress intensity. As the increase of exposure duration, the critic antioxidant substances content and enzyme activities increased first and then maintained a relatively stable higher level. Our findings provide comprehensive information on biochemical responses of hairgrass to hydrological change, which would be a major step for accelerating ecological restoration of degradation alpine marshes in the Qinghai-Tibetan Plateau.

Luo, Qiaoyu↗

DOE OSTI2025

Structural Insights into the Dynamics of Water in SOD1 Catalysis and Drug Interactions

Superoxide dismutase 1 (SOD1) is a crucial enzyme that protects cells from oxidative damage by converting superoxide radicals into H 2 O 2 and O 2 . This detoxification process, essential for cellular homeostasis, relies on a precisely orchestrated catalytic mechanism involving the copper cation, while the zinc cation contributes to the structural integrity of the enzyme. This study presents the 2.3 Å crystal structure of human SOD1 (PDB ID: 9IYK), revealing an assembly of six homodimers and twelve distinct active sites. The water molecules form a complex hydrogen-bonding network that drives proton transfer and sustains active site dynamics. Our structure also uncovers subtle conformational changes that highlight the intrinsic flexibility of SOD1, which is essential for its function. Additionally, we observe how these dynamic structural features may be linked to pathological mutations associated with amyotrophic lateral sclerosis (ALS). By advancing our understanding of hSOD1’s mechanistic intricacies and the influence of water coordination, this study offers valuable insights for developing therapeutic strategies targeting ALS. Our structure’s unique conformations and active site interactions illuminate new facets of hSOD1 function, underscoring the critical role of structural dynamics in enzyme catalysis. Moreover, we conducted a molecular docking analysis using SOD1 for potential radical scavengers and Abelson non-receptor tyrosine kinase (c-Abl, Abl1) inhibitors targeting misfolded SOD1 aggregation along with oxidative stress and apoptosis, respectively. The results showed that CHEMBL1075867, a free radical scavenger derivative, showed the most promising docking results and interactions at the binding site of hSOD1, highlighting its promising role for further studies against SOD1-mediated ALS.

60 APPLIED LIFE SCIENCES↗