In vivo inhibition of polyamine oxidase by a spermine analogue, MDL-72527, in tomato exposed to sublethal and lethal salt stress

2017 ◽  
Vol 44 (5) ◽  
pp. 480 ◽  
Author(s):  
Zoltán Takács ◽  
Péter Poór ◽  
Ágnes Szepesi ◽  
Irma Tari
Keyword(s):  
Cell Death ◽  
Salt Stress ◽  
No Production ◽  
Salt Treatment ◽  
Solanum Lycopersicum L ◽  
Mdl 72527 ◽  
Terminal Oxidation ◽  
Reduced Activity ◽  
Polyamine Oxidases

The spermine analogue N1,N4-bis-(2,3-butadienyl)-1,4-butanediamine (MDL-72527), an effective inhibitor of polyamine oxidases (PAOs), triggers a systemic response in tomato (Solanum lycopersicum L.) exposed to sublethal (100 mM) and lethal (250 mM) NaCl concentrations. The accumulation of free polyamines (PAs), the terminal oxidation of PAs by diamine oxidases (DAOs) and PAOs, and the production of H2O2 by PA oxidases depends on the intensity of salt stress. Spermidine and spermine content increased significantly under sublethal salt concentrations, but remained low under lethal salt stress. Along with increased expression of the selected SlDAO1 and SlPAO1 genes in the leaves and roots, respectively, DAO and PAO activities and their product, H2O2, increased and initiated cell death by irreversible loss of electrolytes at 250 mM NaCl. MDL-72527 significantly increased spermine, spermidine and/or putrescine contents as a result of reduced activity of PA oxidases; furthermore, it inhibited H2O2 and NO production during salt treatment. These results indicate that PAO contributed to H2O2 and NO production under salt stress, and the terminal activities of DAO and PAO play a role in cell death induction at 250 mM NaCl. However, the inhibition of PAO by MDL-72527 does not increase the salt tolerance of plants, since electrolyte leakage increased significantly in the presence of the inhibitor.

2-Methoxy-6-Acetyl-7-Methyljuglone (MAM) Induces iNOS/NO-mediated DNA Damage Response through Activation of MAPKs Pathways

2018 ◽  
Vol 18 (6) ◽  
pp. 903-913 ◽  
Author(s):  
Yanan Niu ◽  
Renyikun Yuan ◽  
Hongwei Gao ◽  
Jin-Jian Lu ◽  
Qi Kong ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Cell Death ◽  
Dna Damage Response ◽  
Cancer Progression ◽  
A549 Cells ◽  
No Production ◽  
Damage Response

Background：There are inconsistent reports about the role of Nitric Oxide (NO) in cancer progression and prevention. Quinones demonstrate significant anti-cancer activities both in vitro and in vivo. Objective： We investigated the effect of 2-methoxy-6-acetyl-7-methyljuglone (MAM), a natural naphthoquinone isolated from Polygonum cuspidatum Sieb. et Zucc, on NO generation and its role in DNA damage in cancer cells. Methods: BEL-7402 and A549 cells were cultured and treated with MAM. The NO generation, DNA damage, and protein expression were determined. Results: MAM induced inducible nitric oxide synthase (iNOS)/NO-mediated DNA damage response through activation of MAPKs pathways. MAM induced DNA damage by activating ATM/Chk2. MAM increased iNOS expression, NO production, and MAPKs (JNK1/2, ERK1/2, and p38MAPK) phosphorylation in concentrationand time- dependent manners. Furthermore, iNOS inhibitor 1400W, iNOS siRNA, and NO scavenger hemoglobin (Hb) could significantly reverse MAM-induced DNA damage, ATM/Chk2 activation, NO production, and cell death. In addition, MAPKs inhibitors (SP600125, U0126, and SB203580) reversed MAM-induced cell death and ATM/Chk2 activation. MAM-induced cell death was partially reversed by 1400W and Hb but enhanced by L-arginine. Conclusion: These results suggested that MAM induced iNOS/NO activation and generation mediated by MAPKs pathways, which resulted in DNA damage.

Carbon monoxide protects against the development of experimental necrotizing enterocolitis

2005 ◽  
Vol 289 (3) ◽  
pp. G607-G613 ◽  
Author(s):  
Brian S. Zuckerbraun ◽  
Leo E. Otterbein ◽  
Patricia Boyle ◽  
Ronald Jaffe ◽  
Jeffrey Upperman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Cell Death ◽  
Necrotizing Enterocolitis ◽  
Intestinal Inflammation ◽  
No Production ◽  
Hypoxia Exposure ◽  
Inos Production

Necrotizing enterocolitis (NEC) is a disease of neonates that is increasing in incidence and often results in significant morbidity and mortality. Carbon monoxide (CO), a byproduct of the catabolism of heme, is known to have anti-inflammatory and antiapoptotic properties. In this study, we aimed to demonstrate that inhaled CO protects against the development of intestinal inflammation in a model of experimental NEC as well as decreases enterocyte cell death in vitro. Additionally, we also aimed to demonstrate that CO decreases enterocyte production of inducible nitric oxide synthase (iNOS) and nitric oxide (NO). Neonatal rats were exposed to intermittent hypoxia exposure and formula feeding to induce experimental NEC. Animals randomized to CO treatment were put in an environment containing 0.025% CO for 1 h/day on days 1–3 of life. All animals were killed on day 4 of life. In vitro experiments were performed with IEC-6 cells, a rat enterocyte cell line. Cells were examined for viability, iNOS production, and elaboration of NO. We found that CO diminished levels of serum inflammatory cytokines and nitrites, protected against intestinal inflammation, and decreased ileal iNOS production and protein nitration in a model of experimental NEC. In vitro, CO decreased cytokine- or hypoxia/endotoxin-induced iNOS and NO production. CO also abrogated TNF-α- and actinomycin D-induced apoptosis or hypoxia/endotoxin-induced cell death. In conclusion, 1 h of daily low-dose inhaled CO protected against the development of intestinal inflammation in a model of experimental NEC. iNOS and NO production were decreased by CO both in vivo and in vitro. CO may prove to be a useful clinical adjunct in the treatment of NEC.

Glial cytotoxicity of low doses of cadmium as a model of heavy metal pollution influence on vertebrates

2020 ◽  
Vol 31 (1) ◽  
pp. 3-10
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
A. M. Hahut ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Oxidative Damage ◽  
Cadmium Chloride ◽  
Glioma Cells ◽  
Low Doses ◽  
Genotoxic Effects ◽  
Cadmium Ions

Cadmium is a common transition metal that entails an extremely wide range of toxic effects in humans and animals. The cytotoxicity of cadmium ions and its compounds is due to various genotoxic effects, including both DNA damage and chromosomal aberrations. Some bone diseases, kidney and digestive system diseases are determined as pathologies that are closely associated with cadmium intoxication. In addition, cadmium is included in the list of carcinogens because of its ability to initiate the development of tumors of several forms of cancer under conditions of chronic or acute intoxication. Despite many studies of the effects of cadmium in animal models and cohorts of patients, in which cadmium effects has occurred, its molecular mechanisms of action are not fully understood. The genotoxic effects of cadmium and the induction of programmed cell death have attracted the attention of researchers in the last decade. In recent years, the results obtained for in vivo and in vitro experimental models have shown extremely high cytotoxicity of sublethal concentrations of cadmium and its compounds in various tissues. One of the most studied causes of cadmium cytotoxicity is the development of oxidative stress and associated oxidative damage to macromolecules of lipids, proteins and nucleic acids. Brain cells are most sensitive to oxidative damage and can be a critical target of cadmium cytotoxicity. Thus, oxidative damage caused by cadmium can initiate genotoxicity, programmed cell death and inhibit their viability in the human and animal brains. To test our hypothesis, cadmium cytotoxicity was assessed in vivo in U251 glioma cells through viability determinants and markers of oxidative stress and apoptosis. The result of the cell viability analysis showed the dose-dependent action of cadmium chloride in glioma cells, as well as the generation of oxidative stress (p <0.05). Calculated for 48 hours of exposure, the LD50 was 3.1 μg×ml-1. The rates of apoptotic death of glioma cells also progressively increased depending on the dose of cadmium ions. A high correlation between cadmium concentration and apoptotic response (p <0.01) was found for cells exposed to 3–4 μg×ml-1 cadmium chloride. Moreover, a significant correlation was found between oxidative stress (lipid peroxidation) and induction of apoptosis. The results indicate a strong relationship between the generation of oxidative damage by macromolecules and the initiation of programmed cell death in glial cells under conditions of low doses of cadmium chloride. The presented results show that cadmium ions can induce oxidative damage in brain cells and inhibit their viability through the induction of programmed death. Such effects of cadmium intoxication can be considered as a model of the impact of heavy metal pollution on vertebrates.

scholarly journals TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection

2021 ◽  
Author(s):  
Hongli Zhou ◽  
Minyu Zhou ◽  
Yue Hu ◽  
Yanin Limpanon ◽  
Yubin Ma ◽  
...  
Keyword(s):  
Cell Death ◽  
Enrichment Analysis ◽  
Angiostrongylus Cantonensis ◽  
Gene Set Enrichment Analysis ◽  
Caspase 8 ◽  
Cns Injury ◽  
Vitro Assay ◽  
Tnf Α

AbstractAngiostrongylus cantonensis (AC) can cause severe eosinophilic meningitis or encephalitis in non-permissive hosts accompanied by apoptosis and necroptosis of brain cells. However, the explicit underlying molecular basis of apoptosis and necroptosis upon AC infection has not yet been elucidated. To determine the specific pathways of apoptosis and necroptosis upon AC infection, gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) analysis for gene expression microarray (accession number: GSE159486) of mouse brain infected by AC revealed that TNF-α likely played a central role in the apoptosis and necroptosis in the context of AC infection, which was further confirmed via an in vivo rescue assay after treating with TNF-α inhibitor. The signalling axes involved in apoptosis and necroptosis were investigated via immunoprecipitation and immunoblotting. Immunofluorescence was used to identify the specific cells that underwent apoptosis or necroptosis. The results showed that TNF-α induced apoptosis of astrocytes through the RIP1/FADD/Caspase-8 axis and induced necroptosis of neurons by the RIP3/MLKL signalling pathway. In addition, in vitro assay revealed that TNF-α secretion by microglia increased upon LSA stimulation and caused necroptosis of neurons. The present study provided the first evidence that TNF-α was secreted by microglia stimulated by AC infection, which caused cell death via parallel pathways of astrocyte apoptosis (mediated by the RIP1/FADD/caspase-8 axis) and neuron necroptosis (driven by the RIP3/MLKL complex). Our research comprehensively elucidated the mechanism of cell death after AC infection and provided new insight into targeting TNF-α signalling as a therapeutic strategy for CNS injury.

scholarly journals Assessment of Morpho-Physiological, Biochemical and Antioxidant Responses of Tomato Landraces to Salinity Stress

Plants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 696
Author(s):  
Reem H. Alzahib ◽  
Hussein M. Migdadi ◽  
Abdullah A. Al Ghamdi ◽  
Mona S. Alwahibi ◽  
Abdullah A. Ibrahim ◽  
...  
Keyword(s):  
Salt Stress ◽  
Salinity Stress ◽  
Dry Weight ◽  
Proline Content ◽  
Enzymatic Antioxidants ◽  
Sod Activity ◽  
Carotene Content ◽  
Antioxidants Activity ◽  
Solanum Lycopersicum L ◽  
Salinity Levels

Understanding salt tolerance in tomato (Solanum lycopersicum L.) landraces will facilitate their use in genetic improvement. The study assessed the morpho-physiological variability of Hail tomato landraces in response to different salinity levels at seedling stages and recommended a tomato salt-tolerant landrace for future breeding programs. Three tomato landraces, Hail 548, Hail 747, and Hail 1072 were tested under three salinity levels: 75, 150, and 300 mM NaCl. Salinity stress reduced shoots’ fresh and dry weight by 71% and 72%, and roots were 86.5% and 78.6%, respectively. There was 22% reduced chlorophyll content, carotene content by 18.6%, and anthocyanin by 41.1%. Proline content increased for stressed treatments. The 300 mM NaCl treatment recorded the most proline content increases (67.37 mg/g fresh weight), with a percent increase in proline reaching 61.67% in Hail 747. Superoxide dismutase (SOD) activity decreased by 65% in Hail 548, while it relatively increased in Hail 747 and Hail 1072 treated with 300 mM NaCl. Catalase (CAT) activity was enhanced by salt stress in Hail 548 and recorded 7.6%, increasing at 75 and 5.1% at 300 mM NaCl. It revealed a reduction in malondialdehyde (MDA) at the 300 mM NaCl concentration in both Hail 548 and Hail 1072 landraces. Increasing salt concentrations showed a reduction in transpiration rate of 70.55%, 7.13% in stomatal conductance, and 72.34% in photosynthetic rate. K+/Na+ ratios decreased from 56% for 75 mM NaCl to 85% for 300 mM NaCl treatments in all genotypes. The response to salt stress in landraces involved some modifications in morphology, physiology, and metabolism. The landrace Hail 548 may have better protection against salt stress and observed protection against reactive oxygen species (ROS) by increasing enzymatic “antioxidants” activity under salt stress.

scholarly journals iPLA2β Contributes to ER Stress-Induced Apoptosis during Myocardial Ischemia/Reperfusion Injury

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1446
Author(s):  
Tingting Jin ◽  
Jun Lin ◽  
Yingchao Gong ◽  
Xukun Bi ◽  
Shasha Hu ◽  
...  
Keyword(s):  
Cell Death ◽  
Heart Disease ◽  
Myocardial Ischemia ◽  
Ischemic Heart Disease ◽  
Er Stress ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion ◽  
Induced Apoptosis

Both calcium-independent phospholipase A2 beta (iPLA2β) and endoplasmic reticulum (ER) stress regulate important pathophysiological processes including inflammation, calcium homeostasis and apoptosis. However, their roles in ischemic heart disease are poorly understood. Here, we show that the expression of iPLA2β is increased during myocardial ischemia/reperfusion (I/R) injury, concomitant with the induction of ER stress and the upregulation of cell death. We further show that the levels of iPLA2β in serum collected from acute myocardial infarction (AMI) patients and in samples collected from both in vivo and in vitro I/R injury models are significantly elevated. Further, iPLA2β knockout mice and siRNA mediated iPLA2β knockdown are employed to evaluate the ER stress and cell apoptosis during I/R injury. Additionally, cell surface protein biotinylation and immunofluorescence assays are used to trace and locate iPLA2β. Our data demonstrate the increase of iPLA2β augments ER stress and enhances cardiomyocyte apoptosis during I/R injury in vitro and in vivo. Inhibition of iPLA2β ameliorates ER stress and decreases cell death. Mechanistically, iPLA2β promotes ER stress and apoptosis by translocating to ER upon myocardial I/R injury. Together, our study suggests iPLA2β contributes to ER stress-induced apoptosis during myocardial I/R injury, which may serve as a potential therapeutic target against ischemic heart disease.

scholarly journals YAP inhibits autophagy and promotes progression of colorectal cancer via upregulating Bcl-2 expression

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Lan Jin ◽  
Yunhe Chen ◽  
Dan Cheng ◽  
Zhikai He ◽  
Xinyi Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Transcriptional Coactivator ◽  
Inhibitory Protein ◽  
Potential Therapeutic Target ◽  
Related Cell ◽  
Autophagy Inhibition

AbstractColorectal cancer (CRC) is one of the most aggressive and lethal cancers. The role of autophagy in the pathobiology of CRC is intricate, with opposing functions manifested in different cellular contexts. The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor-suppressor pathway, functions as an oncoprotein in a variety of cancers. In this study, we found that YAP could negatively regulate autophagy in CRC cells, and consequently, promote tumor progression of CRC in vitro and in vivo. Mechanistically, YAP interacts with TEAD forming a complex to upregulate the transcription of the apoptosis-inhibitory protein Bcl-2, which may subsequently facilitate cell survival by suppressing autophagy-related cell death; silencing Bcl-2 expression could alleviate YAP-induced autophagy inhibition without affecting YAP expression. Collectively, our data provide evidence for YAP/Bcl-2 as a potential therapeutic target for drug exploration against CRC.

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