ROS Signaling Research Articles

Mercury Content and Amelioration of Its Toxicity by Nitric Oxide in Lichens.

Mercury (Hg) content measured in five epiphytic lichen species collected in Slovakia mountain forests ranged from 30 to 100 ng/g DW and was species-specific, decreasing in the order Hypogymnia > Pseudevernia > Usnea > Xanthoria > Evernia prunastri (but polluted sites had no impact on Hg amount in Xanthoria). Evernia was therefore used to study the impact of short-term exogenous Hg (100 µM, 24 h) and possible amelioration of Hg toxicity by nitric oxide (NO) donor sodium nitroprusside (SNP). NO was efficiently released from SNP as detected by two staining reagents and fluorescence microscopy and reduced Hg-induced ROS signal and absorption of Hg by thalli of Evernia prunastri. At the same time, NO ameliorated Hg-induced depletion of metabolites such as ascorbic acid and non-protein thiols, but not of free amino acids. The amount of metabolites, including soluble phenols, was reduced by excess Hg per se. On the contrary, NO was unable to restore Hg-stimulated depletion of chlorophyll autofluorescence but mitigated the decline of some macronutrients (K and Ca). Data confirm that accumulation of Hg in the epiphytic lichens is species-specific and that NO is a vital molecule in Evernia prunastri that provides protection against Hg-induced toxicity with considerable positive impact on metabolic changes.

An Update on Phytochemicals in Redox Homeostasis: “Virtuous or Evil” in Cancer Chemoprevention?

Redox homeostasis, a dynamic process ensuring a balance between cellular oxidizing and reducing reactions, is crucial for maintaining healthy cellular physiology and regulating many biological processes, requiring continuous monitoring and fine-tuning. Reactive species play a critical role in intra/intercellular signaling, and each cell has a specific system guarding cellular redox homeostasis. ROS signaling and oxidative stress are involved in cancer initiation and progression. However, the generation of reactive species beyond the threshold level inside the tumor microenvironment is considered one of the therapeutic approaches. Various studies have shown that some phytochemicals can target the redox homeostasis of the tumor microenvironment. Recent advances have focused on developing and introducing phytochemical interventions as favorable therapeutic options against cancer. However, studies have also suggested the “virtuous” and “evil” impacts of phytochemicals. Some phytochemicals enhance therapeutic efficacy by promoting intracellular oxidant accumulation. However, under certain conditions, some phytochemicals may harm the cellular microenvironment to promote cancer and tend to target different pathways for cancer initiation and development instead of targeting redox homeostasis. In this context, this review is focused on providing an overall understanding of redox homeostasis and intends to highlight the potential positive and negative impacts of phytochemicals in redox homeostasis and disease development. We also discuss the recent nanotechnology-based advancements in combating cancer development.

Physiological and Transcriptomic Analyses Revealed That Humic Acids Improve Low-Temperature Stress Tolerance in Zucchini (Cucurbita pepo L.) Seedlings.

Zucchini (Cucurbita pepo L.) is one of the main vegetable crops grown under protected cultivation in northern China. Low-temperature (LT) stress severely inhibits the growth of zucchini seedlings, resulting in reductions in yield and quality. Here, using three kinds of different humic acids, including coal-based humic acid (CHA), fulvic acid (FA), and biochemical humic acid (BHA), we investigated the effects of humic acids against LT stress (5 °C) in zucchini seedlings. Treatment with all three kinds of humic acids improves LT stress tolerance by decreasing oxidative damage through increases in antioxidative enzyme activities and the contents of soluble sugar and proline in zucchini seedlings, especially after BHA application. Comparative transcriptomic analysis revealed that a total of 17 differentially expressed genes (DEGs) were commonly induced in the leaves of FA-, CHA-, and BHA-treated zucchini seedlings under LT stress, including calmodulin, ethylene-responsive transcription factors (TFs), peroxidases, and 10 TFs, including two NAC and seven WRKY genes. Altogether, these results indicated that supplementation with humic acids reprograms plant metabolism and modulates the expression of genes involved in ROS scavenging, phytohormone metabolism, or signaling pathways, finally improving LT stress tolerance in zucchini seedlings.

ROS and JA signaling participate in positive regulation of Pyrus betulifolia LysM-containing receptor protein 1 (PbeLYP1) in Valsa canker resistance

ROS and JA signaling participate in positive regulation of Pyrus betulifolia LysM-containing receptor protein 1 (PbeLYP1) in Valsa canker resistance

Transcriptome Profiling Reveals Candidate Genes Related to Stipe Gradient Elongation of Flammulina filiformis.

Stipe gradient elongation is an important and remarkable feature in the development of most mushroom fruiting bodies. However, its molecular mechanism has rarely been described. Here, the decreasing trend of stipe elongation and increasing trend of cell length in a gradient from the top to the base of the stipe were determined in a model basidiomycete mushroom: Flammulina filiformis. According to RNA-seq results, 1409 differentially expressed genes (DEGs) were identified among elongation region (ER), transition region (TR), and stable region (SR) samples, including 26 transcription factors (TFs). Based on Short Time-series Expression Miner (STEM) clustering of DEGs, clusters 1 and 3, with obvious expression trends that were consistent with or in contrast to the elongation rate, were screened. The cluster 1 DEGs were mainly involved in the GO cellular component category and KEGG genetic information processing class; however, the cluster 3 DEGs were mainly involved in metabolic processes. Furthermore, qRT-PCR confirmed that key genes of the long-chain fatty acid synthesis pathway were involved in stipe gradient elongation and regulated by NADPH oxidase-derived ROS signaling molecules. These findings provide an essential basis for understanding the molecular mechanism of stipe gradient elongation.

Gene fusions, micro-exons and splice variants define stress signaling by AP2/ERF and WRKY transcription factors in the sesame pan-genome.

Evolutionary dynamics of AP2/ERF and WRKY genes, the major components of defense response were studied extensively in the sesame pan-genome. Massive variation was observed for gene copy numbers, genome location, domain structure, exon-intron structure and protein parameters. In the pan-genome, 63% of AP2/ERF members were devoid of introns whereas >99% of WRKY genes contained multiple introns. AP2 subfamily was found to be micro-exon rich with the adjoining intronic sequences sharing sequence similarity to many stress-responsive and fatty acid metabolism genes. WRKY family included extensive multi-domain gene fusions where the additional domains significantly enhanced gene and exonic sizes as well as gene copy numbers. The fusion genes were found to have roles in acquired immunity, stress response, cell and membrane integrity as well as ROS signaling. The individual genomes shared extensive synteny and collinearity although ecological adaptation was evident among the Chinese and Indian accessions. Significant positive selection effects were noticed for both micro-exon and multi-domain genes. Splice variants with changes in acceptor, donor and branch sites were common and 6-7 splice variants were detected per gene. The study ascertained vital roles of lipid metabolism and chlorophyll biosynthesis in the defense response and stress signaling pathways. 60% of the studied genes localized in the nucleus while 20% preferred chloroplast. Unique cis-element distribution was noticed in the upstream promoter region with MYB and STRE in WRKY genes while MYC was present in the AP2/ERF genes. Intron-less genes exhibited great diversity in the promoter sequences wherein the predominance of dosage effect indicated variable gene expression levels. Mimicking the NBS-LRR genes, a chloroplast localized WRKY gene, Swetha_24868, with additional domains of chorismate mutase, cAMP and voltage-dependent potassium channel was found to act as a master regulator of defense signaling, triggering immunity and reducing ROS levels.

Renoprotective effect of N-acetylcystein and vitamin E in bisphenol A-induced rat nephrotoxicity; Modulators of Nrf2/ NF-κB and ROS signaling pathway.

Bisphenol A (BPA) is a chemical product that is widely used as a plastic precursor. It acts directly on the kidney mitochondria, causing renal dysfunction. N-acetylcysteine is effective in protecting the kidneys from chemical-induced damage. Vitamin E is an antioxidant that protects cells from the damaging effects of free radicals.The aim of this study is to further evaluate and compare NAC and vitamin E to oppose the nephrotoxicity caused by BPA. Forty-two adult male rats were divided into 7 groups: control, BPA, NAC, vitamin E, BPA plus NAC, BPA plus vitamin E, and combined BPA, NAC and vitamin E. BPA, NAC, vitamin E were given orally at doses of 50 mg/kg, 200 mg/kg, and 1000 mg/kg respectively, for 5 weeks. NAC and vitamin E groups showed improved kidney function tests and alleviated BPA-induced oxidative stress; increased GSH and decreased MDA, NO and iNOS levels. NAC and vitamin E significantly attenuated inflammation; decreased NF-κB and increased IL-4, and Nrf2, in addition there was alleviation of renal histopathology. To some extent, vitamin E administration showed significant improvement. Moreover, combined NAC and vitamin E treatment showed more significance than either NAC or vitamin E separate groups. This study determined the substantial protective effects of NAC and/or vitamin E in BPA-induced nephrotoxicity through modulation of Nrf2 with subsequent improvement of oxidative stress and inflammation. The alleviation was more significant in combined NAC and vitamin E treatment mainly through their synergistic effect on Nrf2.

Quercetin rapidly potentiates the biogenesis of nanoselenium via orchestrating key signaling pathways in Chlorella vulgaris

Microalgae are emerging as smart green cell factories for biochemical production and pollutant removal. However, few reports are available on potentiating the algal systems to synthesize selenium nanoparticles (SeNPs), particularly, molecular mechanisms underpinning this biotransformation are yet to be dissected. The Chlorella vulgaris is potentiated by fortifying quercetin (Qn) to facilitate the biotransformation of SeNPs. Quercetin rapidly enhanced the SeNPs formation within 72 hrs from 50 μg/L Na2SeO3 by facilitating the intracellular electron transfer flow, with almost 97 % conversion of inorganic selenite to SeNPs. Electron microscopic analysis of the SeNPs with diameters ranging from 100 nm to 200 nm corroborated the biogenic ability of algal systems. Quercetin fortification obviated the physiological impairments in C. vulgaris induced by selenite in a dose-dependent manner; importantly, Qn-provision significantly enhanced the algal growth rate than the Se-treated cells. Moreover, Qn-treatment altered the fatty acid profile of the total lipids accumulated in C. vulgaris. Transcriptomic analysis showed that quercetin regulated the expression of critical metabolic candidates involved in the Se-assimilation pathway and ROS signal transduction. The data collectively demonstrate the potential green and eco-friendly strategy to reducing the toxic Se into SeNPs and elucidate the mechanistic role underpinning the quercetin-mediated green SeNP biogenesis.

Histone acetylation functions in the wound-induced spore formation in nori.

The red macroalgae Pyropia yezoensis is one of the most economically important marine crops. In the asexual reproduction process, released archeospores could provide secondary seedling resources in nori farming and be used to establish asexual seeding strategies. We previously found that wounds could induce the somatic cells in sectioned Pyropia thalli to develop into large number of asexual wound-induced spores (WIS) in a short time. Many genes involved in signaling pathways, cell division, cell wall remodeling, etc. exhibited transcriptional variation in this cell fate transition process. However, the regulatory mechanisms controlling gene transcription remain elusive. In this study, we found that suberoylanilide hydroxamic acid (SAHA), the inhibitor of histone deacetylase, strongly repressed WIS formation after wounding. The lack of a sharp increase in HDAC activity after wounding, as well as the hyperacetylated status of histone H3 and H4, were observed in SAHA-treated thalli fragments, thus confirming a histone deacetylation-related epigenetic mechanism of wound-induced cell fate reprogramming. Moreover, histone deacetylation is required in the whole process of WIS formation and release. We further compared the genome-wide transcriptional variations after SAHA treatment. SAHA-responsive genes were identified, including some transcriptional factors, chromatin remodeling complex proteins, protein kinases, etc. Transcription of RBOH genes was also altered by SAHA, and moreover, ROS signals in cut fragments were attenuated, both indicating that the ROS systematic signaling pathway is closely associated with histone deacetylation. Our findings provide insights into the biological significance of dynamic histone acetylation states in WIS formation in P. yezoensis.

Screening of Candidate Genes Associated with Brown Stripe Resistance in Sugarcane via BSR-seq Analysis.

Sugarcane brown stripe (SBS), caused by the fungal pathogen Helminthosporium stenospilum, is one of the most serious threats to sugarcane production. However, its outbreaks and epidemics require suitable climatic conditions, resulting in the inefficient improvement of the SBS resistance by phenotype selection. The sugarcane F1 population of SBS-resistant YT93-159 × SBS-susceptible ROC22 was used for constructing the bulks. Bulked segregant RNA-seq (BSR-seq) was then performed on the parents YT93-159 (T01) and ROC22 (T02), and the opposite bulks of 30 SBS-susceptible individuals mixed bulk (T03) and 30 SBS-resistant individuals mixed bulk (T04) collected from 287 F1 individuals. A total of 170.00 Gb of clean data containing 297,921 SNPs and 70,426 genes were obtained. Differentially expressed genes (DEGs) analysis suggested that 7787 and 5911 DEGs were identified in the parents (T01 vs. T02) and two mixed bulks (T03 vs. T04), respectively. In addition, 25,363 high-quality and credible SNPs were obtained using the genome analysis toolkit GATK for SNP calling. Subsequently, six candidate regions with a total length of 8.72 Mb, which were located in the chromosomes 4B and 7C of sugarcane wild species Saccharum spontaneum, were identified, and 279 genes associated with SBS-resistance were annotated by ED algorithm and ΔSNP-index. Furthermore, the expression profiles of candidate genes were verified by quantitative real-time PCR (qRT-PCR) analysis, and the results showed that eight genes (LRR-RLK, DHAR1, WRKY7, RLK1, BLH4, AK3, CRK34, and NDA2) and seven genes (WRKY31, CIPK2, CKA1, CDPK6, PFK4, CBL2, and PR2) of the 20 tested genes were significantly up-regulated in YT93-159 and ROC22, respectively. Finally, a potential molecular mechanism of sugarcane response to H. stenospilum infection is illustrate that the activations of ROS signaling, MAPK cascade signaling, Ca2+ signaling, ABA signaling, and the ASA-GSH cycle jointly promote the SBS resistance in sugarcane. This study provides abundant gene resources for the SBS resistance breeding in sugarcane.

Metabolic and Oxidative Changes in the Fern Adiantum raddianum upon Foliar Application of Metals

Cadmium (Cd) or nickel (Ni) were applied as a foliar spray (1 µM solution over one month) to mimic air pollution and to monitor metabolic responses and oxidative stress in the pteridophyte species. Exogenous metals did not affect the metal content of the soil and had relatively little effect on the essential elements in leaves or rhizomes. The amounts of Cd and Ni were similar in treated leaves (7.2 µg Cd or 5.3 µg Ni/g DW in mature leaves compared with 0.4 µg Cd or 1.2 µg Ni/g DW in the respective control leaves), but Ni was more abundant in rhizomes (56.6 µg Ni or 3.4 µg Cd/g DW), resulting in a higher Cd translocation and bioaccumulation factor. The theoretical calculation revealed that ca. 4% of Cd and 5.5% of Ni from the applied solution per plant/pot was absorbed. Excess Cd induced stronger ROS production followed by changes in SOD and CAT activities, whereas nitric oxide (NO) stimulation was less intense, as detected by confocal microscopy. The hadrocentric vascular bundles in the petioles also showed higher ROS and NO signals under metal excess. This may be a sign of increased ROS formation, and high correlations were observed. Proteins and amino acids were stimulated by Cd or Ni application in individual organs, whereas phenols and flavonols were almost unaffected. The data suggest that even low levels of exogenous metals induce an oxidative imbalance, although no visible damage is observed, and that the responses of ferns to metals are similar to those of seed plants or algae.

EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling.

EROS (essential for reactive oxygen species) protein is indispensable for expression of gp91phox, the catalytic core of the phagocyte NADPH oxidase. EROS deficiency in humans is a novel cause of the severe immunodeficiency, chronic granulomatous disease, but its mechanism of action was unknown until now. We elucidate the role of EROS, showing it acts at the earliest stages of gp91phox maturation. It binds the immature 58 kDa gp91phox directly, preventing gp91phox degradation and allowing glycosylation via the oligosaccharyltransferase machinery and the incorporation of the heme prosthetic groups essential for catalysis. EROS also regulates the purine receptors P2X7 and P2X1 through direct interactions, and P2X7 is almost absent in EROS-deficient mouse and human primary cells. Accordingly, lack of murine EROS results in markedly abnormal P2X7 signalling, inflammasome activation, and T cell responses. The loss of both ROS and P2X7 signalling leads to resistance to influenza infection in mice. Our work identifies EROS as a highly selective chaperone for key proteins in innate and adaptive immunity and a rheostat for immunity to infection. It has profound implications for our understanding of immune physiology, ROS dysregulation, and possibly gene therapy.

Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the Hippocampus.

Microgravity (modeled by head-tilt bedrest and hind-limb unloading), experienced during prolonged spaceflight, results in neurological consequences, central nervous system (CNS) dysfunction, and potentially impairment during the performance of critical tasks. Similar pathologies are observed in bedrest, sedentary lifestyle, and muscle disuse on Earth. In our previous study, we saw that head-tilt bedrest together with social isolation upregulated the milieu of pro-inflammatory cytokines in the hippocampus and plasma. These changes were mitigated in a MCAT mouse model overexpressing human catalase in the mitochondria, pointing out the importance of ROS signaling in this stress response. Here, we used a head-tilt model in socially housed mice to tease out the effects of head-tilt bedrest without isolation. In order to find the underlying molecular mechanisms that provoked the cytokine response, we measured CD68, an indicator of microglial activation in the hippocampus, as well as changes in normal in-cage behavior. We hypothesized that hindlimb unloading (HU) will elicit microglial hippocampal activations, which will be mitigated in the MCAT ROS-quenching mice model. Indeed, we saw an elevation of the activated microglia CD68 marker following HU in the hippocampus, and this pathology was mitigated in MCAT mice. Additionally, we identified cytokines in the hippocampus, which had significant positive correlations with CD68 and negative correlations with exploratory behaviors, indicating a link between neuroinflammation and behavioral consequences. Unveiling a correlation between molecular and behavioral changes could reveal a biomarker indicative of these responses and could also result in a potential target for the treatment and prevention of cognitive changes following long space missions and/or muscle disuse on Earth.

Abstract 15143: The Sphk1/S1P/S1PR2 Axis Regulates Pulmonary Vascular Remodeling by Activating a Mitochondrial ROS and NLRP3 Inflammasome Regulatory Loop

Introduction: Sphk1/S1P/S1PR2 axis regulated NLRP3 inflammasome and promoted pyroptosis by activating NF-κB in human PASMC. Abnormal or inappropriate ROS mediates the development of PAH modulating inflammation, proliferation, and energy metabolism. Mitochondrial ROS promotes deubiquitylation of NLRP3 and activate the inflammasome. However, the function and regulation of S1P axis mediated mitochondrial ROS and NLRP3 inflammasome in PAH remain unknown. Hypothesis: We hypothesized that S1P axis regulated pulmonary vascular remodeling by activated mitochondrial ROS and NLRP3 inflammasome. Methods: NLRP3 inflammasome and pyroptosis activation were detected in PASMC from patients with PAH. JTE013, PF543, MCC950 and MitoTEMPO were used to modulate S1P, NLRP3 inflammasome and mitochondrial ROS signaling, respectively. Activation of inflammasome and pyroptosis were detected by western blots (WB), real-time PCR or immunofluorescence (IF). IL-1β secretion was detected by ELISA. ROS were measured by Mitosox Red and DCFDA. Mitochondrial membrane potential was determined by JC-1 dye assay. PASMCs which were isolated from Sphk1 fl/fl Tagln Cre (+) and Sphk1 fl/fl mice were used to detect the role of S1P axis in vivo. Results: NLRP3 Inflammasome and pyroptosis were activated in PASMCs from patients with PAH. JTE013 or PF543 treatment inhibited NLRP3, ASC, N-GSDMD, HMGB1, cleaved IL-1β and IL-18 expression, and suppressed mitochondrial ROS, as well as mitochondrial hyperpolarization induced by S1P. Treatment with MitoTEMPO decreased S1P induced-NLRP3, ASC, N-GSDMD, HMGB1, cleaved IL-1β and IL-18 expression and inhibited IL-1β secretion. MCC950 controlled the activation of mitochondrial ROS, as well as mitochondrial hyperpolarization which were activated by S1P. NLRP3, cleaved IL-1β, ASC, HMGB1 and N-GSDMD expression were decreased in mPASMCs from Sphk1 fl/fl Tagln Cre (+) mice. Conclusions: S1P induces activation of mitochondrial ROS and NLRP3 inflammasome, and that the Sphk1/S1P/S1PR2 signaling axis may be involved in this context. Activation of the mitochondrial ROS and NLRP3 inflammasome regulatory loop may be an important mechanism underlying PAH pathogenesis, targeting of which may be exploited for the treatment of PAH.

The effects of cannabidiol on ROS signalling and cytokine/chemokine production in mature C2C12 myotubes

The effects of cannabidiol on ROS signalling and cytokine/chemokine production in mature C2C12 myotubes

Overexpression of ZmSRG7 Improves Drought and Salt Tolerance in Maize (Zea mays L.)

Osmotic stress caused by drought and high salinity is the key factor limiting plant growth. However, its underlying molecular regulatory mechanism remains unclear. In this study, we found the stress-related gene Zm00001d019704 (ZmSRG7) based on transcriptome sequencing results previously obtained in the laboratory and determined its biological function in maize. We found that ZmSRG7 was significantly expressed in both roots and leaves under 10% PEG6000 or 150 mM NaCl. Subcellular localization showed that the gene was localized in the nucleus. The germination rate and root length of the ZmSRG7 overexpressing lines were significantly increased under drought or salt stress compared with the control. However, after drought stress, the survival rate and relative water content of maize were increased, while the water loss rate was slowed down. Under salt stress, the Na+ concentration and Na+: K+ ratio of maize was increased. In addition, the contents of antioxidant enzymes and proline in maize under drought or salt stress were higher than those in the control, while the contents of MDA, H2O2 and O2- were lower than those in the control. The results showed that the ZmSRG7 gene played its biological function by regulating the ROS signaling pathway. An interaction between ZmSRG7 and the Zmdhn1 protein was found using a yeast two-hybrid experiment. These results suggest that the ZmSRG7 gene can improve maize tolerance to drought or salt by regulating hydrogen peroxide homeostasis.

Genome wide identification of AGC kinase genes and their expression in response to heat and cold stresses in barley

AGC kinases are highly conserved regulators in a variety of cellular processes such as differentiation, proliferation, and growth. They are known to play important roles in stress and hormonal responses, including ROS signaling. AGC kinases are the main class of protein kinases in plants, having central functions in different stages of plant growth. In the present study, the analysis of phylogenetic relationships, gene structures, chromosomal locations, synteny analysis, gene ontology, subcellular localization, and gene expression of AGC kinase identified 28 AGC kinase genes in barley. Phylogenetic tree grouped them into seven subfamilies, as supported by exon-intron organization. Gene duplication and synteny indicated that tandom and block duplication events played an essential role in the expansion of AGC kinase gene families in barley. The Real-time quantitative reverse transcription PCR (qRT-PCR) analysis performed for HvAGC kinase gene were largely expressed in different tissues of roots, stems, and leaves in Azaran and Jolgeh cultivars under heat and cold stresses. The results of chromosomal localization showed that the AGC kinases were located on all chromosomes of barley except chromosome 1. Genome evolution of species was surveyed using identification of orthologous and paralogous genes. Identifying overlaps between orthologous clusters can enable us to study the function and evolution of proteins in different species. To our knowledge, this is the first detailed report of using AGC kinases for bioinformatics analysis in barley. Results revealed a broad understanding of the AGC kinase gene family in barley, which will be valuable for improving barley varieties’ response to heat and cold stresses. Also, HvNDR6.2 gene can utilized as molecular markers under cold stress in the three organs.

Genetic identification of SNP markers and candidate genes associated with sugarcane smut resistance using BSR-Seq.

Sugarcane smut caused by Sporisorium scitamineum is one of the most severe fungal diseases worldwide. In this study, a cross was made between a smut-resistant variety YT93-159 and a smut-susceptible variety ROC22, and 312 progenies were obtained. Two bulks of progenies were then constructed, one consisted of 27 highly smut resistant progenies and the other 24 smut susceptible progenies. Total RNAs of the progenies of each bulk, were pooled and subject to bulked segregant RNA-sequence analysis (BSR-Seq). A total of 164.44 Gb clean data containing 2,341,449 SNPs and 64,999 genes were obtained, 7,295 of which were differentially expressed genes (DEGs). These DEGs were mainly enriched in stress-related metabolic pathways, including carbon metabolism, phenylalanine metabolism, plant hormone signal transduction, glutathione metabolism, and plant-pathogen interactions. Besides, 45,946 high-quality, credible SNPs, a 1.27 Mb region at Saccharum spontaneum chromosome Chr5B (68,904,827 to 70,172,982), and 129 candidate genes were identified to be associated with smut resistance. Among them, twenty-four genes, either encoding key enzymes involved in signaling pathways or being transcription factors, were found to be very closely associated with stress resistance. RT-qPCR analysis demonstrated that they played a positive role in smut resistance. Finally, a potential molecular mechanism of sugarcane and S. scitamineum interaction is depicted that activations of MAPK cascade signaling, ROS signaling, Ca2+ signaling, and PAL metabolic pathway and initiation of the glyoxalase system jointly promote the resistance to S. scitamineum in sugarcane. This study provides potential SNP markers and candidate gene resources for smut resistance breeding in sugarcane.

Mitochondria-Associated Molecular Mechanisms in Endometriosis - A Mini Review

Endometriosis is a multifaceted disorder, with a variety of factors and processes at play. Research is currently investigating the influence of genetics, epigenetics, signaling pathways, and oxidative stress in its etiology. It is clear that these elements have an effect on the mitochondria in different cells, which are responsible for regulating ROS production, energy metabolism, and signal transduction in endometriosis. An assessment of mitochondrial-related molecular mechanisms in endometriosis is in progress.

Regulation of serine palmitoyl-transferase and Rac1–Nox2 signaling in diabetic retinopathy

Hyperlipidemia is considered as one of the major systemic factors associated with the development of diabetic retinopathy, and animal models have documented that its presence in a hyperglycemic environment exacerbates cytosolic ROS production (via activation of the Rac1–Nox2 axis) and mitochondrial damage. Hyperglycemia also accelerates Rac1 transcription via dynamic DNA methylation–hydroxymethylation of its promoter. In diabetes, ceramide metabolism in the retina is impaired and its accumulation is increased. Our aim was to investigate the effect of inhibition of the rate limiting enzyme of the de novo ceramide biosynthesis, serine palmitoyl-transferase (SPT), on Rac1 activation in diabetic retinopathy. Using human retinal endothelial cells, transfected with SPT-siRNA, and incubated in 20 mM d-glucose in the presence or absence of 50 µM palmitate (glucolipotoxic and glucotoxic, respectively), activities of Rac1 and Nox2, and ROS levels were quantified. For Rac1 transcriptional activation, 5 hydroxymethyl cytosine (5hmC) levels at its promoter were quantified. Key parameters were confirmed in retinal microvessels from streptozotocin-induced diabetic mice on a normal diet (type 1 diabetic model) or on a high-fat diet (45% kcal, type 2 diabetic model), injected intravitreally with SPT-siRNA. Compared to normal glucose, cells in high glucose, with or without palmitic acid, had increased Rac1–Nox2–ROS signaling, Rac1 transcripts and 5hmC levels at its promoter. Inhibition of SPT by SPT-siRNA or myriocin prevented glucotoxic- and glucolipotoxic-induced increase in Rac1–Nox2–ROS signaling and 5hmC at the Rac1 promoter. Similarly, in both type 1 and type 2 diabetic mouse models, SPT-siRNA attenuated the increase in the Rac1–Nox2–ROS axis and 5hmC at the Rac1 promoter. Thus, inhibition of the rate limiting enzyme of ceramide de novo biosynthesis, SPT, regulates activation of DNA methylation–hydroxymethylation machinery and prevents increased Rac1 transcription. This ameliorates the activation of Rac1–Nox2 signaling and protects the mitochondria from damaging cytosolic ROS, which prevents accelerated capillary cell loss. These results further raise the importance of regulating lipid levels in diabetic patients with dyslipidemia.