scholarly journals The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1

2019 ◽  
Vol 20 (20) ◽  
pp. 5225 ◽  
Author(s):  
Ssu-Yu Chen ◽  
Shu-Ting Liu ◽  
Wun-Rong Lin ◽  
Chi-Kang Lin ◽  
Shih-Ming Huang
Keyword(s):  
Copper Sulfate ◽  
Hela Cells ◽  
Stress Proteins ◽  
Hypoxia Inducible Factor ◽  
Human Kidney ◽  
Ros Generation ◽  
Ros Production ◽  
Cytotoxic Effects ◽  
Functional Roles ◽  
Normal Human Kidney

Copper is an essential trace element within cells, but it also exerts cytotoxic effects through induction of reactive oxygen species (ROS) production. To determine the mechanisms underlying copper-induced ROS production, we examined the effects of copper sulfate in HeLa cells. Exposure to copper sulfate led to dose-dependent decreases in HeLa cell viability, along with increases in the subG1 and G2/M populations and corresponding decreases in the G1 population. Copper sulfate also increased the levels of apoptosis, senescence, mitochondrial dysfunction, autophagy, ROS, and the expression of several stress proteins, including ATF3, c-Fos, DEC1 (differentiated embryonic chondrocyte gene 1), p21, p53, and HIF-1α (hypoxia-inducible factor 1 alpha). The suppression of copper-induced ROS generation by the ROS scavenger N-acetyl cysteine verified copper’s functional role, while the suppression of copper’s effects by the copper chelator disulfiram, confirmed its specificity. Selective induction of HIF-1α, p53, and phosphorylated ERK proteins by copper was blocked by the knockdown of the transcription factor DEC1, suggesting copper’s effects are mediated by DEC1. In addition to HeLa cells, copper also exerted cytotoxic effects in human endometrial (HEC-1-A) and lung (A549) adenocarcinoma cells, but not in normal human kidney (HEK293) or bronchial (Beas-2B) epithelial cells. These findings shed new light on the functional roles of copper within cells.

scholarly journals Reactive Oxygen Species in Host Plant Are Required for an Early Defense Response against Attack of Stagonospora nodorum Berk. Necrotrophic Effectors SnTox

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1586
Author(s):  
Svetlana Veselova ◽  
Tatyana Nuzhnaya ◽  
Guzel Burkhanova ◽  
Sergey Rumyantsev ◽  
Igor Maksimov
Keyword(s):  
Reactive Oxygen Species ◽  
Early Stage ◽  
Reactive Oxygen ◽  
Triticum Aestivum L ◽  
Redox Status ◽  
Stagonospora Nodorum ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Necrotrophic Effectors

Reactive oxygen species (ROS) play a central role in plant immune responses. The most important virulence factors of the Stagonospora nodorum Berk. are multiple fungal necrotrophic effectors (NEs) (SnTox) that affect the redox-status and cause necrosis and/or chlorosis in wheat lines possessing dominant susceptibility genes (Snn). However, the effect of NEs on ROS generation at the early stages of infection has not been studied. We studied the early stage of infection of various wheat genotypes with S nodorum isolates -Sn4VD, SnB, and Sn9MN, carrying a different set of NE genes. Our results indicate that all three NEs of SnToxA, SnTox1, SnTox3 significantly contributed to cause disease, and the virulence of the isolates depended on their differential expression in plants (Triticum aestivum L.). The Tsn1–SnToxA, Snn1–SnTox1and Snn3–SnTox3 interactions played an important role in inhibition ROS production at the initial stage of infection. The Snn3–SnTox3 inhibited ROS production in wheat by affecting NADPH-oxidases, peroxidases, superoxide dismutase and catalase. The Tsn1–SnToxA inhibited ROS production in wheat by affecting peroxidases and catalase. The Snn1–SnTox1 inhibited the production of ROS in wheat by mainly affecting a peroxidase. Collectively, these results show that the inverse gene-for gene interactions between effector of pathogen and product of host sensitivity gene suppress the host’s own PAMP-triggered immunity pathway, resulting in NE-triggered susceptibility (NETS). These results are fundamentally changing our understanding of the development of this economical important wheat disease.

scholarly journals Evaluation of Cytotoxic Effects of Dichloromethane Extract of Guduchi (Tinospora cordifolia Miers ex Hook F & THOMS) on Cultured HeLa Cells

2006 ◽  
Vol 3 (2) ◽  
pp. 267-272 ◽  
Author(s):  
Ganesh Chandra Jagetia ◽  
Shaival Kamalaksha Rao
Keyword(s):  
Lipid Peroxidation ◽  
Lactate Dehydrogenase ◽  
Hela Cells ◽  
Cytotoxic Effect ◽  
Tinospora Cordifolia ◽  
Cytotoxic Effects ◽  
Optimal Duration ◽  
Ldh Release ◽  
Gst Activity

Extracts ofTinospora cordifolia(TCE) have been shown to possess anti-tumor properties, but the mechanism of the anti-tumor function of TCE is poorly understood. This investigation elucidates the possible mechanism underlying the cytotoxic effects of dichlormethane extracts of TCE, after selecting optimal duration and concentration for treatment. HeLa cells were exposed to various concentrations of TCE, which has resulted in a concentration-dependent decline in the clonogenicity, glutathione-S-transferase (GST) activity and a concentration-dependent increase in lipid peroxidation (TBARS) with a peak at 4 h and lactate dehydrogenase (LDH) release with a peak at 2 h. Our results suggest that the cytotoxic effect of TCE may be due to lipid peroxidation and release of LDH and decline in GST.

scholarly journals Biosynthesis of Complement C4 Messenger RNA in Normal Human Kidney

Nephron ◽  
1989 ◽  
Vol 53 (4) ◽  
pp. 338-342 ◽  
Author(s):  
H.E. Feucht ◽  
J. Zwirner ◽  
D. Bevec ◽  
Margot Lang ◽  
E. Felber ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Human Kidney ◽  
Complement C4 ◽  
Normal Human Kidney ◽  
Normal Human

Oxidative stress augments pulmonary hypertension in chronically hypoxic mice overexpressing the oxidized LDL receptor

2013 ◽  
Vol 305 (2) ◽  
pp. H155-H162 ◽  
Author(s):  
Sayoko Ogura ◽  
Tatsuo Shimosawa ◽  
ShengYu Mu ◽  
Takashi Sonobe ◽  
Fumiko Kawakami-Mori ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ros Generation ◽  
Low Density ◽  
Ros Production ◽  
Oxidized Low Density Lipoprotein

Chronic hypoxia is one of the main causes of pulmonary hypertension (PH) associated with ROS production. Lectin-like oxidized low-density lipoprotein receptor (LOX)-1 is known to be an endothelial receptor of oxidized low-density lipoprotein, which is assumed to play a role in the initiation of ROS generation. We investigated the role of LOX-1 and ROS generation in PH and vascular remodeling in LOX-1 transgenic (TG) mice. We maintained 8- to 10-wk-old male LOX-1 TG mice and wild-type (WT) mice in normoxia (room air) or hypoxia (10% O2 chambers) for 3 wk. Right ventricular (RV) systolic pressure (RVSP) was comparable between the two groups under normoxic conditions; however, chronic hypoxia significantly increased RVSP and RV hypertrophy in LOX-1 TG mice compared with WT mice. Medial wall thickness of the pulmonary arteries was significantly greater in LOX-1 TG mice than in WT mice. Furthermore, hypoxia enhanced ROS production and nitrotyrosine expression in LOX-1 TG mice, supporting the observed pathological changes. Administration of the NADPH oxidase inhibitor apocynin caused a significant reduction in PH and vascular remodeling in LOX-1 TG mice. Our results suggest that LOX-1-ROS generation induces the development and progression of PH.

scholarly journals Different expression of the plasminogen activation system in renal thrombotic microangiopathy and the normal human kidney

1996 ◽  
Vol 50 (6) ◽  
pp. 2011-2019 ◽  
Author(s):  
Yichun Xu ◽  
Jacqueline Hagege ◽  
Béatrice Mougenot ◽  
Jean-Daniel Sraer ◽  
Ebbe Rønne ◽  
...  
Keyword(s):  
Thrombotic Microangiopathy ◽  
Human Kidney ◽  
Plasminogen Activation ◽  
Plasminogen Activation System ◽  
Normal Human Kidney ◽  
Activation System ◽  
Normal Human

TOXOHORMONE IN BACTERIA-FREE TUMORS

1966 ◽  
Vol 44 (8) ◽  
pp. 1069-1087 ◽  
Author(s):  
J. C. Nixon ◽  
B. Zinman
Keyword(s):  
Gel Filtration ◽  
Human Kidney ◽  
Metastatic Carcinoma ◽  
Exchange Chromatography ◽  
Human Spleen ◽  
Normal Tissues ◽  
Highly Active ◽  
Normal Human Kidney ◽  
Tumor Tissues ◽  
Normal Human

Toxohormone was extracted from bacteria-free human tumors and normal tissues, and assayed for activity by measuring the decrease in serum iron levels of rats 12 hours after injection of the extracts. In contrast with the findings of others, the results of the present study demonstrated that active toxohormone could be isolated from bacteria-free tumor tissues. Bacteria-free normal human kidney and spleen also yielded active toxohormone extracts, whereas extracts of normal human- and rat-skeletal muscle and rat liver had no activity.Four active toxohormone extracts were purified by ion-exchange chromatography followed by gel filtration. Human leukemic spleen, metastatic carcinoma of the cecum, and normal human spleen and kidney yielded several highly active purified fractions.

scholarly journals Diabetes potentiates ROS production in granulocytes from patients with chronic kidney disease

2021 ◽  
Vol 9 (1) ◽  
pp. 9-14
Author(s):  
Jose Augusto Nogueira-Machado ◽  
Gabriela Rossi Ferreira ◽  
Caroline Maria Oliveira Volpe ◽  
Pedro Henrique Villar-Delfino ◽  
Fabiana Rocha Silva
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Nadph Oxidase ◽  
Ros Generation ◽  
Ros Production ◽  
Clinical Prognosis ◽  
Before And After ◽  
Healthy Control ◽  
Toll Receptor

Background: Type 2 diabetes (DM2) and chronic kidney disease (CKD) are inflammatory pathologies. Diabetes is characterized by hyperglycemia and CKD by the gradual and irreversible loss of kidney function. Both diseases develop oxidative stress, and reactive oxygen species (ROS) play a pivotal role in the pathogenesis. This study aimed to determine ROS production by granulocytes from renal patients (CKD) with or without diabetes. Methods: Granulocytes from patients with DM2, CKD, CKD-DM2, and healthy controls were purified using the Ficoll-Hypaque gradient method. Granulocyte ROS generation in the absence or the presence of PDB (an activator of NADPH-oxidase) or Concanavalin A (Toll- receptor 3,9 activator) was evaluated in a luminol-dependent chemiluminescence method. The cell-free DNA in the serum of DM2, CKD, and CKD-DM2 patients was measured by the fluorescence method before and after hemodialysis. Results: Our results show a significant increase in ROS production by granulocytes from patients with CKD, DM2, and CKD-DM2 compared to healthy control (p<0.05). CKD-DM2 group produced the most significant ROS levels with or without NADPH-oxidase activation. ROS production showed a significant increase in the presence of ConA. In contrast, mitochondrial (internal) ROS showed a different ROS response. DNA extrusion was higher in the CKD-DM2 group after hemodialysis suggesting cell death. Conclusion: The results demonstrated that CKD-DM2 patients produced high ROS generation levels and increased DNA extrusion after hemodialysis. It may suggest that CKD-DM2 disease is more severe and has a worse clinical prognosis.

scholarly journals Potential mechanisms of quantitative resistance to Leptosphaeria maculans (blackleg) on cotyledons of canola (Brassica napus)

2020 ◽  
Author(s):  
Michelle Hubbard ◽  
Chun Zhai ◽  
Gary Peng
Keyword(s):  
Signal Transduction ◽  
Cell Death ◽  
Fluorescent Protein ◽  
Quantitative Resistance ◽  
Leptosphaeria Maculans ◽  
Small Gtpases ◽  
Ros Generation ◽  
Ros Production ◽  
Potential Marker ◽  
Starting Point

Abstract Background: Blackleg disease, caused by Leptosphaeria maculans (Lm), can lead to significant losses of canola/rapeseed crops. Growing resistant canola cultivars can be an effective and environmentally friendly way to manage blackleg. Major resistance genes may stop infection, but can also be rapidly overcome by shifts in pathogen population towards virulence. Thus, using race-nonspecific or quantitative resistance (QR) is of interest because it is potentially more durable. However, the mechanisms and genes underlying QR are mostly unknown. In this study, we explored QR in “74‑44 BL”, a Canadian canola cultivar carrying a moderate level of race nonspecific resistance, based on cotyledon inoculation (Supple. Fig.1) . The susceptible cultivar “Westar” was used as a control. Lesions developed more slowly on 74-44BL than on Westar. We used RNA-Seq to identify genes and gene functions putatively involved in the QR. Results: Relative to inoculated Westar, some of the B. napus genes that were differentially expressed strongly in inoculated 74-44 BL included those putatively involved in programmed cell death (PCD), reactive oxygen species (ROS) generation, signal transduction and/or intracellular endomembrane transport. Examples included genes annotated as a Bax inhibitor 1, a development/cell death (DCD) domain containing proteinases and peptidases, all of which could play a role in PCD and a zinc-finger Sec23/Sec24 and five small GTPases likely involved in endoplasmic reticulum (ER) to Golgi vesicle traffic and/or signal transduction. Further experiments, however, did not confirm changes in genomic DNA degradation, a potential marker for PCD, between the two cultivars. In addition, infection progression in cotyledons was not altered by applying protease inhibitors directly to cotyledons. Additional testing was done using green fluorescent protein (GFP)-tagged Lm for cotyledon colonization as well as ROS production, in relation to the lesion development. The results showed that ROS production occurred beyond the area colonized by Lm hyphae in 74-44 BL.Conclusions: ROS may also be involved in signal transduction and/or intracellular endomembrane transport. These results provide a starting point for a better understanding of the mechanisms behind QR against Lm in canola and developing new host-resistance strategies for management of blackleg.

scholarly journals Cellular receptors for matrix proteins in normal human kidney and human mesangial cells

1990 ◽  
Vol 38 (5) ◽  
pp. 886-895 ◽  
Author(s):  
Fernando G. Cosio ◽  
Daniel D. Sedmak ◽  
N. Stanley Nahman
Keyword(s):  
Mesangial Cells ◽  
Human Kidney ◽  
Matrix Proteins ◽  
Cellular Receptors ◽  
Human Mesangial Cells ◽  
Normal Human Kidney ◽  
Normal Human
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