ROS Metabolism Research Articles

Mechanisms of Cancer-killing by Quercetin; A Review on Cell Death Mechanisms.

Cancer drug resistance has always been a serious issue regarding cancer research and therapy. Different cancers undergo different mutations, which may cause suppression of tumor suppressor genes, inhibition of apoptosis, stimulation of drug resistance mediators, and exhaustion of the immune system. The modulation of pro-death and survival-related mediators is an intriguing strategy for cancer therapy. Several nature-derived molecules, e.g., quercetin, have shown interesting properties against cancer through the modulation of apoptosis and autophagy mediators. Such molecules, e.g., quercetin, have been shown to stimulate apoptosis and other types of cell death pathways in cancers via the modulation of ROS metabolism. Quercetin may affect immune system function and trigger the expression and activity of tumor suppressor genes. Furthermore, it may suppress certain multidrug resistance mechanisms in cancer cells. This paper aims to review the effects of quercetin on various cell death mechanisms such as apoptosis, autophagic cell death, senescence, ferroptosis, and others.

Different cold tolerances among three strains of large yellow croaker: related to antioxidant defense and energy metabolism

The aim of this study was to compare low-temperature tolerances in different strains of large yellow croaker. Dai Qu (DQ), Min-Yue Dong (MY), and Quan Zhou (NZ) strains of large yellow croaker were subjected to cold stress (8.6°C) for 12h, 24h, 48h, and 96h. Survival rate, histological observation, and antioxidant and energy metabolism indicators were determined. The results showed that compared with the DQ group and MY group, NZ group aggravated hepatic structure, enhanced ROS, lactate, and anaerobic metabolism (PK gene expression and activity), while inhibited ATP, GSH, antioxidant enzymes (mRNA levels and activities of SOD, GPx, and CAT), and aerobic metabolism enzymes (mRNA levels and activities of F-ATPase, SDH, and MDH), indicating the reduction of cold tolerance in the NZ group was closely correlated with the decrement of antioxidative capacity and energy metabolism efficiency. Nrf2 and AMPK gene expressions were correlated with antioxidant and energy metabolism mRNA levels, respectively, suggesting Nrf2 and AMPK might participate in the modulation of target genes during the cold-stress adaptation. In conclusion, low temperature tolerance of fish depended on the antioxidant defense and energy metabolism efficiency, which contributes to understanding the underlying mechanisms of cold adaptation in large yellow croaker.

Mitochondrial Dysfunction, Altered Mitochondrial Oxygen, and Energy Metabolism Associated with the Pathogenesis of Schizophrenia.

The significant complexity of the brain can lead to the development of serious neuropsychiatric disorders, including schizophrenia. A number of mechanisms are involved in the etiopathogenesis of schizophrenia, pointing to its complexity and opening a new perspective on studying this disorder. In this review of currently published studies, we focused on the contribution of mitochondria to the process, with an emphasis on oxidative damage, ROS, and energy metabolism. In addition, we point out the influence of redox imbalance, which can lead to the occurrence of oxidative stress with increased lipid peroxidation, linked to the formation of toxic aldehydes such as 4-hydroxynonenal (4-HNE) and HNE protein adducts. We also analysed the role of lactate in the process of energy metabolism and cognitive functions in schizophrenia.

Different Cutting Methods Affect the Quality of Fresh-Cut Cucumbers by Regulating ROS Metabolism

Fresh-cut cucumbers (Cucumis sativus L.) are appreciated by consumers for their convenience and freshness. In the process of home cooking and in the food industry, different cutting methods for cucumbers are needed. In order to explore the effect of cutting methods on the quality of fresh-cut cucumbers, cucumbers were cut into slices, pieces, and strips and whole cucumbers were used as the control. The results indicate that the vitamin C content of the sliced, pieced, and stripped cucumbers was gradually reduced, while the glutathione content increased significantly (p < 0.05) compared with the whole cucumbers. Furthermore, this study reveals that the fresh-cutting operation induced the production of ROS (O2−· and H2O2). Simultaneously, cutting activates phenylalanine ammonia-lyase and peroxidase activity, which enhanced the total phenol content by 1.35 times, 1.51 times, and 1.78 times in the pieced, stripped, and sliced cucumbers, respectively. This combines with the enhancement in the ascorbate peroxidase, glutathione reductase, superoxide dismutase, and catalase activity, contributing to the antioxidant capacity increasing by 1.14–1.95 times compared with the control. In conclusion, the degree of quality indexes was sliced > pieced > stripped. Therefore, this study provides useful information to illuminate the mechanism of the quality change in fresh-cut cucumbers subjected to different cutting methods and makes suggestions on the appropriate cutting style for the commercial or home use of cucumbers.

Abstract 613: T cell antitumor function requires potassium transport

Abstract Background: The past 20 years of translational oncology provide a framework in which the ability to eradicate cancer has increased in direct relation to our understanding of T cell biology. The cancer-killing functions of T cells are often compromised within tumors, allowing disease progression. Tumor-derived factors and the hostile microenvironment contribute to constraining of T cell effector functions and driving terminal differentiation. We previously identified that elevated extracellular K+ characteristics of the tumor microenvironment limits both TCR dependent activation and effector functions, while preserving coincidently preserving T cell stemness (Eil R, Nature 2016 & Science 2019). Despite these findings and the centrality of ion gradients to cellular physiology broadly, our understanding of T cell K+ transport remains rudimentary and cannot account for the pleiotropic role K+ abundance plays in antitumor immunity. In fact, little is known about what K+ transporters T cell express nor their functional regulation. Findings: Here, we report the canonical Na+-K+-ATPase to be intertwined with T cell metabolic homeostasis, memory formation, and antitumor activity and therefore an appealing avenue for T cell reprogramming. We first performed whole-transcriptomic sequencing of CD8+ memory subsets and found that components of the Na+-K+-ATPase were expressed at robust levels that were notably enriched in naïve and memory cells. Despite partially impairing Ca2+ influx, T cells genetically deficient for the Na+-K+-ATPase exhibited constitutive activity in both TCR and Akt-mTOR associated signaling pathways along with rapid acquisition of co-inhibitory surface receptors, mitotic arrest, and functional exhaustion. Mechanistically, we identified pathologic ROS accumulation as the driver of unregulated signaling and rapid exhaustion. In vivo, T cells lacking deficient in Na+-K+-ATPase activity failed to achieve proliferative burst following pathogen challenge and demonstrated severely compromised antitumor function. Our results support a model in which the Na+- K+- ATPase primarily functions in T cells to maintain ROS metabolism, thereby preventing its pathologic accumulation and preserving T cell stemness and antitumor potential. Conclusion: These results uncover a fundamental yet underappreciated aspect of T cell biology with translational implications for the ongoing development of cancer immunotherapies. Immediate applications include pharmacologic and genetic targeting of ion transporters in the setting of immune checkpoint blockade or T cell transfer therapies (i.e. CAR, TCR, TIL). Citation Format: Camille Collier, Matthew McWhorter, Kelly Wucherer, Chelsea Jenkins, Alexandra Bartlett, Robert Eil. T cell antitumor function requires potassium transport [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 613.

MAPK cascade and ROS metabolism are involved in GABA-induced disease resistance in red pitaya fruit

This study investigates the effects of γ-Aminobutyric acid (GABA) and mitogen-activated protein kinase (MAPK) inhibitor (PD98059) in disease resistance in red pitaya fruit. Results demonstrated that GABA treatment suppressed the growth of Gilbertella persicaria; increased H2O2 content and O2•- production rate; enhanced reduced glutathione and ascorbic acid contents, as well as increased the activities and transcripts of catalase (CAT), NADPH oxidase (NOX), peroxidise (POD), superoxide dismutase (SOD), ascorbate peroxidase (APX) and glutathione reductase (GR), and up-regulated HcMYB111/24 expressions. Furthermore, GABA promoted the expressions of HcMAPKKK1-HcMAPKK2/4-HcMAPK1/7 cascades. However, PD98059 +GABA treatment decreased the disease resistance against G. persicaria and reduced H2O2 content; inhibited the activities and gene expressions of NOX, CAT, SOD, POD, GR and APX, and down-regulated the expressions of HcMAPK1/7. These findings suggest that GABA induces disease resistance by regulating ROS metabolism and MAPK cascades in red pitaya fruit.

The photosynthetic function analysis for leaf photooxidation in rice

Photooxidative damage causes early leaf senescence and plant cell death. In this study, a light-sensitive rice cultivar, 812HS, and a non-light-sensitive cultivar, 812S, were used to investigate early leaf photooxidation. Leaf tips of 812HS exhibited yellowing under a light intensity of 720 µmol(photon) m-2 s-1, accompanied by a decrease in chlorophyll and carotenoids, but 812S was unaffected. The photosynthetic performance of 812HS was also poorer than that of 812S. The H2O2, O2*-, and malondialdehyde content increased sharply in 812HS, and associated antioxidant enzymes were inhibited. The degradation of core proteins in both PSI and PSII, as well as other photosynthesis-related proteins, was accelerated in 812HS. When shaded [180 µmol(photon) m-2 s-1], 812HS recovered to normal. Therefore, our findings suggested excess light disturbed the balance of ROS metabolism, leading to the destruction of the antioxidant system and photosynthetic organs, and thus triggering the senescence of rice leaves.

Insights into strigolactone (GR24) mediated regulation of cadmium-induced changes and ROS metabolism in Artemisia annua

Agricultural soil contamination and subsequently crops still require alternative solutions to reduce associated environmental risks. The effects of strigolactones (SLs) in alleviating cadmium (Cd) phytotoxicity in Artemisia annua plants were investigated during this study. Strigolactones play a vital role during plant growth and development due to their complex interplay during a plethora of biochemical processes. However, information on the potential of SLs to elicit abiotic stress signaling and trigger physiological modifications in plants is limited. In order to decipher the same, A. annua plants were exposed to different concentrations of Cd (20 and 40 mg kg-1), with or without the supplementation of exogenous SL (GR24, a SL analogue) at 4 µM concentration. Under Cd stress, excess Cd accumulation resulted in reduced growth, physio-biochemical traits, and artemisinin content. However, the follow-up treatment of GR24 maintained a steady state equilibrium between reactive oxygen species and antioxidant enzymes, improved chlorophyll fluorescence parameters such as Fv/Fm, ФPSII, and ETR for improved photosynthesis, enhanced chlorophyll content, maintained chloroplast ultrastructure, improved the glandular trichome (GT) attributes and artemisinin production in A. annua. Moreover, it also resulted in improved membrane stability, reduced Cd accumulation, and regulated the behaviour of stomatal apertures for better stomatal conductance under Cd stress. The results of our study suggest that GR24 could be highly effective in alleviating Cd-induced damages in A. annua. It acts via the modulation of the antioxidant enzyme system for redox homeostasis, protection of the chloroplasts and pigments for improved photosynthetic performance, and improved GT attributes for enhanced artemisinin production in A. annua.

Zeolitic Imidazolate Framework-8 Triggers the Inhibition of Arginine Biosynthesis to Combat Methicillin-Resistant Staphylococcus Aureus.

The self-preservation and intelligent survival abilities of methicillin-resistant Staphylococcus aureus (MRSA) result in the ineffective treatment of many antibiotics. Nano-drug delivery systems have emerged as a new strategy to overcome MRSA infection. ZIF-8 nanoparticles (ZIF-8 NPs) exhibit good antibacterial activities, while its molecular mechanisms are largely elusive. In this study, the ZIF-8 NPs are prepared using the room temperature solution reaction method. The values of minimum inhibitory concentration of ZIF-8 NPs against Escherichia coli and MRSA isolates are 25 and 12.5µg mL-1 , respectively. Transcriptome and metabonomic analyses reveal that ZIF-8 NPs could trigger the inhibition of arginine biosynthesis pathway and the production of ROS, which lead to dysfunctional tricarboxylic acid cycle and disruption of cell membrane integrity, eventually killing MRSA isolates. Moreover, ZIF-8 NPs show desirable treatment and repair effects on mice model of MRSA isolates wound infected-model. The results, for the first time, reveal that the inhibition of arginine biosynthesis mediates the production of ROS and energy metabolism dysfunction contributes to the antibacterial ability of ZIF-8 NPs against MRSA. This study offers a new insight into ZIF-8 NPs combating MRSA isolates.

BHLH57 confers chilling tolerance and grain yield improvement in rice.

Chilling stress has become a major limiting factor that reduces crop productivity worldwide. In this study, we identified a new gene bHLH57, whose product enhances chilling tolerance in rice at diverse developmental stages. bHLH57 was mainly expressed in leaves and anthers, and its protein was targeted to the nucleus. Overexpression of bHLH57 enhanced chilling tolerance by increasing trehalose synthesis, whereas its mutants by CRISPR/Cas9-mediated mutagenesis were more sensitive to chilling and had reduced trehalose. Meanwhile, bHLH57 may regulate ROS metabolism and CBFs/DREBs- dependent pathways in response to chilling stress. In addition, the overexpression of bHLH57 resulted in increased grain yield under normal and chilling conditions, however, the disruption of bHLH57 displayed decreased grain size and seed setting rate, thus reduced grain yield. Phylogenetic and nucleotide diversity analyses suggested that bHLH57 is relatively conserved in monocotyledons, and may be selected during indica populations adaptation. Taken together, we have identified a new bHLH regulator involved rice chilling tolerance and grain yield, and provide a potential target gene for improving chilling tolerance and grain yield of rice.

The uppermost monoterpenes improving Cinnamomum camphora thermotolerance by serving signaling functions.

Terpenes serve important functions in enhancing plant thermotolerance. Cinnamomum camphora mainly has eucalyptol (EuL), camphor (CmR), linalool (LnL) and borneol (BeL) chemotypes basing on the uppermost monoterpenes. To reveal the thermotolerance mechanisms of these uppermost monoterpenes (eucalyptol, camphor, linalool, and borneol) in C. camphora, we surveyed the ROS metabolism and photosynthesis in the 4 chemotypes fumigated with the corresponding uppermost monoterpene after fosmidomycin (Fos) inhibiting monoterpene synthesis under high temperature at 38°C (Fos+38°C+monoterpene), and investigated the related gene expression in EuL and CmR. Meanwhile, the thermotolerance differences among the 4 uppermost monoterpenes were analyzed. In contrast to normal temperature (28°C), ROS levels and antioxidant enzyme activities in the 4 chemotypes increased under 38°C, and further increased in the treatment with Fos inhibiting monoterpene synthesis at 38°C (Fos+38°C), which may be caused by the alterations in expression of the genes related with non-enzymatic and enzymatic antioxidant formation according to the analyses in EuL and CmR. Compared with Fos+38°C treatment, Fos+38°C+monoterpene treatments lowered ROS levels and antioxidant enzyme activities for the increased non-enzymatic antioxidant gene expression and decreased enzymatic antioxidant gene expression, respectively. High temperature at 38°C reduced the chlorophyll and carotenoid content as well as photosynthetic abilities, which may result from the declined expression of the genes associated with photosynthetic pigment biosynthesis, light reaction, and carbon fixation. Fos+38°C treatment aggravated the reduction. In contrast to Fos+38°C treatment, Fos+38°C+monoterpene treatments increased photosynthetic pigment content and improved photosynthetic abilities by up-regulating related gene expression. Among the 4 uppermost monoterpenes, camphor showed strong abilities in lowering ROS and maintaining photosynthesis, while eucalyptol showed weak abilities. This was consistent with the recovery effects of the gene expression in the treatments with camphor and eucalyptol fumigation. Therefore, the uppermost monoterpenes can enhance C. camphora thermotolerance as signaling molecules, and may have differences in the signaling functions.

Comparative transcriptome analyses shed light on the regulation of harvest duration and shelf life in sweet corn

Harvest duration and postharvest shelf life are two of the most important characters for sweet corn. However, the regulatory mechanism remains unclear. We performed a comparative transcriptome analysis of long harvest-duration and shelf-life sweet corn (LHS) and short harvest-duration and shelf-life field corn (SHS) at three stages, i.e. 10 days after pollination (10DAP), 22 days after pollination (22DAP), and 7 days after harvest (7DAH). We have observed the major transcriptome changes accompanying the harvest process in LHS corn. Gene expression pattern analysis and differentially expressed genes (DEGs) functional enrichments suggested an association between ROS metabolism in kernels with harvest duration and postharvest shelf life. The genes encoding cytochrome P450, peroxidase, peroxiredoxin, glutathione peroxidase, and glutathione S-transferase were upregulated specifically in LHS kernels during and after harvest compared to SHS kernels. These novel findings reveal a new regulatory mechanism of corn post-harvest shelf life and should be useful for extending harvest duration and shelf life for sweet corn.

Radiation Type- and Dose-Specific Transcriptional Responses across Healthy and Diseased Mammalian Tissues.

Ionizing radiation (IR) is a genuine genotoxic agent and a major modality in cancer treatment. IR disrupts DNA sequences and exerts mutagenic and/or cytotoxic properties that not only alter critical cellular functions but also impact tissues proximal and distal to the irradiated site. Unveiling the molecular events governing the diverse effects of IR at the cellular and organismal levels is relevant for both radiotherapy and radiation protection. Herein, we address changes in the expression of mammalian genes induced after the exposure of a wide range of tissues to various radiation types with distinct biophysical characteristics. First, we constructed a publicly available database, termed RadBioBase, which will be updated at regular intervals. RadBioBase includes comprehensive transcriptomes of mammalian cells across healthy and diseased tissues that respond to a range of radiation types and doses. Pertinent information was derived from a hybrid analysis based on stringent literature mining and transcriptomic studies. An integrative bioinformatics methodology, including functional enrichment analysis and machine learning techniques, was employed to unveil the characteristic biological pathways related to specific radiation types and their association with various diseases. We found that the effects of high linear energy transfer (LET) radiation on cell transcriptomes significantly differ from those caused by low LET and are consistent with immunomodulation, inflammation, oxidative stress responses and cell death. The transcriptome changes also depend on the dose since low doses up to 0.5 Gy are related with cytokine cascades, while higher doses with ROS metabolism. We additionally identified distinct gene signatures for different types of radiation. Overall, our data suggest that different radiation types and doses can trigger distinct trajectories of cell-intrinsic and cell-extrinsic pathways that hold promise to be manipulated toward improving radiotherapy efficiency and reducing systemic radiotoxicities.

Phytochromes and Their Role in Diurnal Variations of ROS Metabolism and Plant Proteome.

Plants are sessile organisms forced to adapt to environmental variations recurring in a day-night cycle. Extensive research has uncovered the transcriptional control of plants' inner clock and has revealed at least some part of the intricate and elaborate regulatory mechanisms that govern plant diel responses and provide adaptation to the ever-changing environment. Here, we analyzed the proteome of the Arabidopsis thaliana mutant genotypes collected in the middle of the day and the middle of the night, including four mutants in the phytochrome (phyA, phyB, phyC, and phyD) and the circadian clock protein LHY. Our approach provided a novel insight into the diel regulations, identifying 640 significant changes in the night-day protein abundance. The comparison with previous studies confirmed that a large portion of identified proteins was a known target of diurnal regulation. However, more than 300 were novel oscillations hidden under standard growth chamber conditions or not manifested in the wild type. Our results indicated a prominent role for ROS metabolism and phytohormone cytokinin in the observed regulations, and the consecutive analyses confirmed that. The cytokinin signaling significantly increased at night, and in the mutants, the hydrogen peroxide content was lower, and the night-day variation seemed to be lost in the phyD genotype. Furthermore, regulations in the lhy and phyB mutants were partially similar to those found in the catalase mutant cat2, indicating shared ROS-mediated signaling pathways. Our data also shed light on the role of the relatively poorly characterized Phytochrome D, pointing to its connection to glutathione metabolism and the regulation of glutathione S-transferases.

ROS Regulate NCF2, Key Metabolic Enzymes and MDA Levels to Affect the Growth of Fusarium solani

Fusarium solani is the most significant pathogen that causes root rot in wolfberry, which has led to serious economic losses in terms of production. As an important enzyme in organisms, NADPH oxidase produces ROS. However, the mechanism of ROS mediated by NADPH oxidase in the growth of F. solani has not been studied. In this study, F. solani colonies were treated with 40 µmol/L DPI and 0.0012% H2O2. The growth rate in terms of colonies, number of spores, key gene expression levels, activity of key enzymes and the content of key products of ROS metabolic pathways were determined. The results showed that the growth rate of colonies treated by DPI decreased by 19.43%, the number of macroconidia increased by 231.03%, the IOD/area values of O2− and H2O2 decreased by 34.88% and 16.97%, respectively, the expression levels in terms of NCF2, SOD1, CTA1 and PXMP4 significantly decreased and the activities of SOD, CAT and POD decreased significantly, while the MDA content increased significantly. Additionally, in the case of the colonies treated with exogenous H2O2, the MDA content decreased significantly while the other indicators increased. Taken together, the NCF2 gene is involved in regulating the activity of NADPH oxidase and regulates the products of O2− and ROS metabolism enzyme genes and their activities to affect colony growth in the F. solani growth process.

The allelopathic effect of para-hydroxybenzoic acid on the gene expression of photosynthesis and respiration in Solanum lycopersicum

As an important economically and nutritionally valuable vegetable, tomato has been planted everywhere worldwide, which has resulted in a succession cropping obstacle due to the shortage of farmland. The effects of plant allelopathy, one of the major obstacles to succession cropping, has not been fully defined or explored, especially on plant gene expression profile changes. In this study, the high-throughput sequencing technology was used to analysis the gene expression in tomato leaves treated with the Para-hydroxybenzoic acid (PHBA), an important allelochemical, that was found to have the highest content in the soil of succession cropped tomatoes. We found the expression of genes related to respiration, photosynthesis, starch and sucrose metabolism, amino acid metabolism, pyrimidine metabolism, and ROS metabolism was changed in response to PHBA treatment. Our study on the allelopathic effects of PHBA on photosynthesis and respiration in Solanum lycopersicum has provided a solid evidence for the negative effect of allelochemical on the transcriptomic profiles needed for normal physiological activities of succession cropped tomato, thus will be beneficial for improving our knowledge of the mechanism of plant allelopathy.

Transcriptome Analysis Reveals Genes and Pathways Associated with Salt Tolerance during Seed Germination in Suaeda liaotungensis.

Seed germination is susceptible to external environmental factors, especially salt stress. Suaeda liaotungensis is a halophyte with strong salt tolerance, and the germination rate of brown seeds under 1000 mM NaCl treatment still reached 28.9%. To explore the mechanism of salt stress response during brown seed germination in Suaeda liaotungensis, we conducted transcriptomic analysis on the dry seeds (SlD), germinated seeds under the control condition (SlG_C), and salt treatment (SlG_N). Transcriptome analysis revealed that 13314 and 755 differentially expressed genes (DEGs) from SlD vs. SlG_C and SlG_C vs. SlG_N were detected, respectively. Most DEGs were enriched in pathways related to transcription regulation and hormone signal transduction, ROS metabolism, cell wall organization or biogenesis, and carbohydrate metabolic process in two contrasting groups. Compared with the control condition, POD and CAT activity, H2O2, soluble sugar, and proline contents were increased during germinated seeds under salt stress. Furthermore, functional analysis demonstrated that overexpression of SlNAC2 significantly enhanced salt tolerance during the germination stage in Arabidopsis. These results not only revealed the tolerant mechanism of brown seed germination in response to salinity stress but also promoted the exploration and application of salt-tolerant gene resources of Suaeda liaotungensis.

LncRNA Hnf4αos exacerbates liver ischemia/reperfusion injury in mice via Hnf4αos/Hnf4α duplex-mediated PGC1α suppression

LncRNAs are involved in the pathophysiologic processes of multiple diseases, but little is known about their functions in hepatic ischemia/reperfusion injury (HIRI). As a novel lncRNA, the pathogenetic significance of hepatic nuclear factor 4 alpha, opposite strand (Hnf4αos) in hepatic I/R injury remains unclear. Here, differentially expressed Hnf4αos and Hnf4α antisense RNA 1 (Hnf4α-as1) were identified in liver tissues from mouse ischemia/reperfusion models and patients who underwent liver resection surgery. Hnf4αos deficiency in Hnf4αos-KO mice led to improved liver function, alleviated the inflammatory response and reduced cell death. Mechanistically, we found a regulatory role of Hnf4αos-KO in ROS metabolism through PGC1α upregulation. Hnf4αos also promoted the stability of Hnf4α mRNA through an RNA/RNA duplex, leading to the transcriptional activation of miR-23a and miR-23a depletion was required for PGC1α function in hepatoprotective effects on HIRI. Together, our findings reveal that Hnf4αos elevation in HIRI leads to severe liver damage via Hnf4αos/Hnf4α/miR-23a axis-mediated PGC1α inhibition.

The transcription factor SlNAP1 increases salt tolerance by modulating ion homeostasis and ROS metabolism in Solanum lycopersicum

NAC transcription factors (TFs) play an important role in the plant resistant response to biotic and abiotic stresses. However, the functions of the most NAC TFs are still unknown, especially in tomato. Here, we identified and functionally characterized an NAC TFs, SlNAP1, in tomato, and found that SlNAP1 was significantly induced by salt stress. Under 150 mM NaCl treatments, morphological indexes of SlNAP1 over-expressed (SlNAP1-OE) transgenic tomato lines were significantly better than the wild-type (WT) plants. The content of Na+ in leaves and roots of SlNAP1-OE transgenic plants decreased, while the K+ content in leaves, roots, and stems increased compared with WT plants. The expression of the salt stress-related genes (NHX1, HKT1;2 and SOS1) in SlNAP1-OE plants were also significantly up-regulated under salt stress. The SOD, POD and CAT activities and the expression level of antioxidant oxidase synthesis genes of SlNAP1-OE lines were significantly increased. In addition, the SlNAP1-OE lines accumulated less MDA, H2O2 and O2•−, improved antioxidant defense systems which contributed to increase salt tolerance. In summary, our data suggest that SlNAP1 positively regulates salt tolerance in tomato by regulating ion homeostasis and ROS metabolism.

YgiM may act as a trigger in the sepsis caused by Klebsiella pneumoniae through the membrane-associated ceRNA network.

Sepsis is one of the diseases that can cause serious mortality. In E. coli, an inner membrane protein YgiM encoded by gene ygiM can target the eukaryotic peroxisome. Peroxisome is a membrane-enclosed organelle associated with the ROS metabolism and was reported to play the key role in immune responses and inflammation during the development of sepsis. Klebsiella pneumoniae (K. pneumoniae) is one of the important pathogens causing sepsis. However, the function of gene vk055_4013 which is highly homologous to ygiM of E. coli has not been demonstrated in K. pneumoniae. In this study, we prepared ΔygiM of K. pneumoniae ATCC43816, and found that the deletion of ygiM did not affect bacterial growth and mouse mortality in the mouse infection model. Interestingly, ΔygiM not only resulted in reduced bacterial resistance to macrophages, but also attenuated pathological manifestations in mouse organs. Furthermore, based on the data of Gene Expression Omnibus, the expression profiles of micro RNAs (miRNAs) and messenger RNAs (mRNAs) in the serum of 44 sepsis patients caused by K. pneumoniae infection were analyzed, and 11 differently expressed miRNAs and 8 DEmRNAs associated with the membrane function were found. Finally, the membrane-associated competing endogenous RNAs (ceRNAs) network was constructed. In this ceRNAs network, DEmiRNAs (hsa-miR-7108-5p, hsa-miR-6780a-5p, hsa-miR-6756-5p, hsa-miR-4433b-3p, hsa-miR-3652, hsa-miR-342-3p, hsa-miR-32-5p) and their potential downstream target DEmRNAs (VNN1, CEACAM8, PGLYRP1) were verified in the cell model infected by wild type and ΔygiM of K. pneumoniae, respectively. Taken together, YgiM may trigger the sepsis caused by K. pneumoniae via membrane-associated ceRNAs. This study provided new insights into the role of YgiM in the process of K. pneumoniae induced sepsis.