Response of two wheat genotype to long-term salinity stress in relation to oxidative stress and osmolyte concentration

AbstractRepeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural and neurobehavioural changes are currently unknown. Here, we utilised an established rat model to investigate the effects of repeated sub-concussion on size of lateral ventricles, cerebrovascular blood–brain barrier (BBB) integrity, neuroinflammation, oxidative stress, and biochemical distribution. Following repeated sub-concussion 3 days per week for 2 weeks, the rats showed significantly enlarged lateral ventricles compared with the rats receiving sham-only procedure. The sub-concussive rats also presented significant BBB dysfunction in the cerebral cortex and hippocampal formation, whilst neuromotor function assessed by beamwalk and rotarod tests were comparable to the sham rats. Immunofluorescent and spectroscopic microscopy analyses revealed no significant changes in neuroinflammation, oxidative stress, lipid distribution or protein aggregation, within the hippocampus and cortex. These data collectively indicate that repeated sub-concussion for 2 weeks induce significant ventriculomegaly and BBB disruption, preceding neuromotor deficits.

Download Full-text

Crosstalk between Long-Term Sublethal Oxidative Stress and Detrimental Inflammation as Potential Drivers for Age-Related Retinal Degeneration

Antioxidants ◽

10.3390/antiox10010025 ◽

2020 ◽

Vol 10 (1) ◽

pp. 25

Author(s):

Lara Macchioni ◽

Davide Chiasserini ◽

Letizia Mezzasoma ◽

Magdalena Davidescu ◽

Pier Luigi Orvietani ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Mechanisms ◽

Age Related Macular Degeneration ◽

Inflammasome Activation ◽

Related Factor ◽

Nuclear Factor ◽

Rpe Cells ◽

Age Related ◽

Oxidative Insult

Age-related retinal degenerations, including age-related macular degeneration (AMD), are caused by the loss of retinal pigmented epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD, deeply linked to the aging process, also involves oxidative stress and inflammatory responses. However, the molecular mechanisms contributing to the shift from healthy aging to AMD are still poorly understood. Since RPE cells in the retina are chronically exposed to a pro-oxidant microenvironment throughout life, we simulated in vivo conditions by growing ARPE-19 cells in the presence of 10 μM H2O2 for several passages. This long-term oxidative insult induced senescence in ARPE-19 cells without affecting cell proliferation. Global proteomic analysis revealed a dysregulated expression in proteins involved in antioxidant response, mitochondrial homeostasis, and extracellular matrix organization. The analyses of mitochondrial functionality showed increased mitochondrial biogenesis and ATP generation and improved response to oxidative stress. The latter, however, was linked to nuclear factor-κB (NF-κB) rather than nuclear factor erythroid 2–related factor 2 (Nrf2) activation. NF-κB hyperactivation also resulted in increased pro-inflammatory cytokines expression and inflammasome activation. Moreover, in response to additional pro-inflammatory insults, senescent ARPE-19 cells underwent an exaggerated inflammatory reaction. Our results indicate senescence as an important link between chronic oxidative insult and detrimental chronic inflammation, with possible future repercussions for therapeutic interventions.

Download Full-text

Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma

Endocrinology ◽

10.1210/en.2018-00014 ◽

2018 ◽

Vol 159 (8) ◽

pp. 2836-2849 ◽

Cited By ~ 8

Author(s):

Vasileios Chortis ◽

Angela E Taylor ◽

Craig L Doig ◽

Mark D Walsh ◽

Eirini Meimaridou ◽

...

Keyword(s):

Oxidative Stress ◽

Adrenocortical Carcinoma ◽

Reduced Form ◽

Polyamine Metabolism ◽

Metabolome Analysis ◽

Nucleotide Synthesis ◽

Treatment Target ◽

Nicotinamide Nucleotide Transhydrogenase ◽

Response To Chemotherapy

Abstract Adrenocortical carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. In this study, we evaluated a potential new treatment target for ACC, focusing on the mitochondrial reduced form of NAD phosphate (NADPH) generator nicotinamide nucleotide transhydrogenase (NNT). NNT has a central role within mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating human NNT mutations result in congenital adrenal insufficiency. We hypothesized that NNT silencing in ACC cells will induce toxic levels of oxidative stress. To explore this, we transiently knocked down NNT in NCI-H295R ACC cells. As predicted, this manipulation increased intracellular levels of oxidative stress; this resulted in a pronounced suppression of cell proliferation and higher apoptotic rates, as well as sensitization of cells to chemically induced oxidative stress. Steroidogenesis was paradoxically stimulated by NNT loss, as demonstrated by mass spectrometry–based steroid profiling. Next, we generated a stable NNT knockdown model in the same cell line to investigate the longer lasting effects of NNT silencing. After long-term culture, cells adapted metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remained suppressed. This was associated with higher rates of oxygen consumption. The molecular pathways underpinning these responses were explored in detail by RNA sequencing and nontargeted metabolome analysis, revealing major alterations in nucleotide synthesis, protein folding, and polyamine metabolism. This study provides preclinical evidence of the therapeutic merit of antioxidant targeting in ACC as well as illuminating the long-term adaptive response of cells to oxidative stress.

Download Full-text

Immunolocalization of antioxidant enzymes in testis of rams submitted to long-term heat stress

Zygote ◽

10.1017/s0967199419000467 ◽

2019 ◽

Vol 27 (6) ◽

pp. 432-435

Author(s):

Thais Rose dos Santos Hamilton ◽

Gabriela Esteves Duarte ◽

José Antonio Visintin ◽

Mayra Elena Ortiz D’Ávila Assumpção

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Antioxidant Enzymes ◽

Heat Stress ◽

Glutathione Peroxidase ◽

Cell Types ◽

Treated Group ◽

Oxidative Balance ◽

Testicular Cells

SummaryLong-term heat stress (HS) induced by testicular insulation generates oxidative stress (OS) on the testicular environment; consequently activating antioxidant enzymes such as superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx). The aim of this work was to immunolocalize antioxidant enzymes present in different cells within the seminiferous tubule when rams were submitted to HS. Rams were divided into control (n = 6) and treated group (n = 6), comprising rams subjected to testicular insulation for 240 h. After the testicular insulation period, rams were subjected to orchiectomy. Testicular fragments were submitted to immunohistochemistry for staining against SOD, GR and GPx enzymes. We observed immunolocalization of GPx in more cell types of the testis after HS and when compared with other enzymes. In conclusion, GPx is the main antioxidant enzyme identified in testicular cells in an attempt to maintain oxidative balance when HS occurs.

Download Full-text

Protection of Italian ryegrass (Lolium multiflorum L.) seedlings from salinity stress following seed priming with L-methionine and casein hydrolysate

Seed Science Research ◽

10.1017/s0960258520000409 ◽

2020 ◽

pp. 1-9

Author(s):

Keum-Ah Lee ◽

Youngnam Kim ◽

Hossein Alizadeh ◽

David W.M. Leung

Keyword(s):

Oxidative Stress ◽

Amino Acids ◽

Salinity Stress ◽

Lolium Multiflorum ◽

Casein Hydrolysate ◽

Seed Priming ◽

Germination Percentage ◽

Italian Ryegrass ◽

Significant Difference ◽

Protein Amino Acids

Abstract Seed priming with water (hydropriming or HP) has been shown to be beneficial for seed germination and plant growth. However, there is little information on the effects of seed priming with amino acids and casein hydrolysate (CH) compared with HP, particularly in relation to early post-germinative seedling growth under salinity stress. In this study, Italian ryegrass seeds (Lolium multiflorum L.) were primed with 1 mM of each of the 20 protein amino acids and CH (200 mg l−1) before they were germinated in 0, 60 and 90 mM NaCl in Petri dishes for 4 d in darkness. Germination percentage (GP), radicle length (RL) and peroxidase (POD) activity in the root of 4-d-old Italian ryegrass seedlings were investigated. Generally, when the seeds were germinated in 0, 60 and 90 mM NaCl, there was no significant difference in GP of seeds among various priming treatments, except that a higher GP was observed in seeds of HP treatment compared with the non-primed seeds when incubated in 60 mM NaCl. When incubated in 60 and 90 mM NaCl, seedlings from seeds primed with L-methionine or CH exhibited greater RL (greater protection against salinity stress) and higher root POD activity than those from non-primed and hydro-primed seeds. Under salinity stress, there were higher levels of malondialdehyde (MDA) in the root of 4-d-old Italian ryegrass seedlings, a marker of oxidative stress, but seed priming with CH was effective in reducing the salinity-triggered increase in MDA content. These results suggest that priming with L-methionine or CH would be better than HP for the protection of seedling root growth under salinity stress and might be associated with enhanced antioxidative defence against salinity-induced oxidative stress.

Download Full-text

Physiological and molecular responses for long term salinity stress in common fig (Ficus carica L.)

Physiology and Molecular Biology of Plants ◽

10.1007/s12298-020-00921-z ◽

2021 ◽

Vol 27 (1) ◽

pp. 107-117

Author(s):

Monther T. Sadder ◽

Ibrahim Alshomali ◽

Ahmad Ateyyeh ◽

Anas Musallam

Keyword(s):

Salinity Stress ◽

Ficus Carica ◽

Molecular Responses ◽

Common Fig

Download Full-text

Cellular stress signaling activates type-I IFN response through FOXO3-regulated lamin posttranslational modification

Nature Communications ◽

10.1038/s41467-020-20839-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Inah Hwang ◽

Hiroki Uchida ◽

Ziwei Dai ◽

Fei Li ◽

Teresa Sanchez ◽

...

Keyword(s):

Oxidative Stress ◽

Environmental Changes ◽

Type I ◽

Neurogenic Differentiation ◽

Forkhead Box ◽

Nuclear Lamin ◽

Neural Stem Progenitor Cells ◽

Subsequent Activation ◽

Methyl Group Transfer

AbstractNeural stem/progenitor cells (NSPCs) persist over the lifespan while encountering constant challenges from age or injury related brain environmental changes like elevated oxidative stress. But how oxidative stress regulates NSPC and its neurogenic differentiation is less clear. Here we report that acutely elevated cellular oxidative stress in NSPCs modulates neurogenic differentiation through induction of Forkhead box protein O3 (FOXO3)-mediated cGAS/STING and type I interferon (IFN-I) responses. We show that oxidative stress activates FOXO3 and its transcriptional target glycine-N-methyltransferase (GNMT) whose upregulation triggers depletion of s-adenosylmethionine (SAM), a key co-substrate involved in methyl group transfer reactions. Mechanistically, we demonstrate that reduced intracellular SAM availability disrupts carboxymethylation and maturation of nuclear lamin, which induce cytosolic release of chromatin fragments and subsequent activation of the cGAS/STING-IFN-I cascade to suppress neurogenic differentiation. Together, our findings suggest the FOXO3-GNMT/SAM-lamin-cGAS/STING-IFN-I signaling cascade as a critical stress response program that regulates long-term regenerative potential.

Download Full-text

Hypermetabolism of glutathione, glutamate and ornithine via redox imbalance in methylglyoxal-induced peritoneal injury rats

The Journal of Biochemistry ◽

10.1093/jb/mvz077 ◽

2019 ◽

Author(s):

Ichiro Hirahara ◽

Eiji Kusano ◽

Denan Jin ◽

Shinji Takai

Keyword(s):

Oxidative Stress ◽

Intraperitoneal Administration ◽

Methionine Sulfoxide ◽

Mesenchymal Cell ◽

Oxidative Stress Marker ◽

Peritoneal Fibrosis ◽

Metabolome Analysis ◽

Glycation End Products ◽

Excessive Proliferation

Abstract Peritoneal dialysis (PD) is a blood purification treatment for patients with reduced renal function. However, the peritoneum is exposed to oxidative stress during PD and long-term PD results in peritoneal damage, leading to the termination of PD. Methylglyoxal (MGO) contained in commercial PD fluids is a source of strong oxidative stress. The aim of this study was to clarify the mechanism of MGO-induced peritoneal injury using metabolome analysis in rats. We prepared peritoneal fibrosis rats by intraperitoneal administration of PD fluids containing MGO for 21 days. As a result, MGO-induced excessive proliferation of mesenchymal cells with an accumulation of advanced glycation end-products (AGEs) at the surface of the thickened peritoneum in rats. The effluent levels of methionine sulfoxide, an oxidative stress marker and glutathione peroxidase activity were increased in the MGO-treated rats. The levels of glutathione, glutamate, aspartate, ornithine and AGEs were also increased in these rats. MGO upregulated the gene expression of transporters and enzymes related to the metabolism of glutathione, glutamate and ornithine in the peritoneum. These results suggest that MGO may induce peritoneal injury with mesenchymal cell proliferation via increased redox metabolism, directly or through the formation of AGEs during PD.

Download Full-text