Nano-CuO causes cell damage through activation of dose-dependent autophagy and mitochondrial lncCyt b-AS/ND5-AS/ND6-AS in SH-SY5Y cells

ABSTRACTThe purpose of the present study was to evaluate the toxicity of voriconazole on cultured human corneal endothelial cells (HCECs). HCECs were cultured and exposed to various concentrations of voriconazole (5.0 to 1,000 μg/ml). Cell viability was measured using a Cell Counting Kit-8 (CCK-8) and live/dead viability/cytotoxicity assays. Cell damage was assessed using phase-contrast microscopy after 24 h of exposure to voriconazole. To analyze the effect of voriconazole on the intercellular barrier, immunolocalization of zonula occludens 1 (ZO1) was performed. A flow cytometric assay was performed to evaluate the apoptotic and necrotic effects of voriconazole on HCECs. Cytotoxicity tests demonstrated the dose-dependent toxic effect of voriconazole on HCECs. Voriconazole concentrations of ≥100 μg/ml led to a significant reduction in cell viability. The morphological characteristics of HCECs also changed in a dose-dependent manner. Increasing concentrations of voriconazole resulted in fading staining for ZO1. Higher concentrations of voriconazole resulted in an increased number of propidium iodide (PI)-positive cells, indicating activation of the proapoptotic pathway. In conclusion, voriconazole may have a dose-dependent toxic effect on cultured HCECs. The results of this study suggest that although voriconazole concentrations of up to 50 μg/ml do not decrease cell viability, intracameral voriconazole concentrations of ≥100 μg/ml may increase the risk of corneal endothelial damage.

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Induction of tissue transglutaminase by dexamethasone: its correlation to receptor number and transglutaminase-mediated cell death in a series of malignant hamster fibrosarcomas

Biochemical Journal ◽

10.1042/bj3310105 ◽

1998 ◽

Vol 331 (1) ◽

pp. 105-112 ◽

Cited By ~ 24

Author(s):

Timothy S. JOHNSON ◽

Claire I. SCHOLFIELD ◽

James PARRY ◽

Martin GRIFFIN

Keyword(s):

Cell Death ◽

Cell Damage ◽

Tissue Transglutaminase ◽

Receptor Protein ◽

Mrna Synthesis ◽

Body Formation ◽

Transglutaminase Activity ◽

Receptor Number ◽

Dose Dependent ◽

Hamster Fibrosarcoma

Treatment of the hamster fibrosarcoma cell lines (Met B, D and E) and BHK-21 hamster fibroblast cells with the glucocorticoid dexamethasone led to a powerful dose-dependent mRNA-synthesis-dependent increase in transglutaminase activity, which can be correlated with dexamethasone-responsive receptor numbers in each cell line. Increasing the number of dexamethasone-responsive receptors by transfection of cells with the HG1 glucocorticoid receptor protein caused an increase in transglutaminase activity that was proportional to the level of transfected receptor. In all experiments the levels of the tissue transglutaminase-mediated detergent-insoluble bodies was found to be comparable with increases in transglutaminase activity. Despite an increase in detergent-insoluble body formation, an increase in apoptosis as measured by DNA fragmentation was not found. Incubation of cells with the non-toxic competitive transglutaminase substrate fluorescein cadaverine led to the incorporation of this fluorescent amine into cellular proteins when cells were damaged after exposure to trypsin during cell passage. These cross-linked proteins containing fluorescein cadaverine were shown to be present in the detergent-insoluble bodies, indicating that the origin of these bodies is via activation of tissue transglutaminase after cell damage by trypsinization rather than apoptosis per se,since Met B cells expressing the bcl-2 cDNA were not protected from detergent-insoluble body formation. We describe a novel mechanism of cell death related to tissue transglutaminase expression and cell damage.

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Akt Downregulation by Flavin Oxidase–Induced ROS Generation Mediates Dose-Dependent Endothelial Cell Damage Elicited by Natural Antioxidants

Toxicological Sciences ◽

10.1093/toxsci/kfp301 ◽

2009 ◽

Vol 114 (1) ◽

pp. 101-112 ◽

Cited By ~ 39

Author(s):

Valeria Pasciu ◽

Anna Maria Posadino ◽

Annalisa Cossu ◽

Bastiano Sanna ◽

Bruna Tadolini ◽

...

Keyword(s):

Endothelial Cell ◽

Cell Damage ◽

Natural Antioxidants ◽

Ros Generation ◽

Endothelial Cell Damage ◽

Dose Dependent

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Exposure to Sub-Lethal Doses of Permethrin Is Associated with Neurotoxicity: Changes in Bioenergetics, Redox Markers, Neuroinflammation and Morphology

Toxics ◽

10.3390/toxics9120337 ◽

2021 ◽

Vol 9 (12) ◽

pp. 337

Author(s):

Teresita Guadalupe López-Aceves ◽

Elvia Coballase-Urrutia ◽

Francisco Estrada-Rojo ◽

América Vanoye-Carlo ◽

Liliana Carmona-Aparicio ◽

...

Keyword(s):

Cell Damage ◽

Brain Regions ◽

Protein Carbonyl ◽

Histopathological Analysis ◽

Synthetic Pyrethroids ◽

Dependent Manner ◽

Mitochondrial Uncoupling ◽

Respiratory Parameters ◽

Species Production ◽

Dose Dependent

Permethrin (PERM) is a member of the class I family of synthetic pyrethroids. Human use has shown that it affects different systems, with wide health dysfunctions. Our aim was to determine bioenergetics, neuroinflammation and morphology changes, as redox markers after subacute exposure to PERM in rats. We used MDA determination, protein carbonyl assay, mitochondrial O2 consumption, expression of pro-inflammatory cytokines and a deep histopathological analysis of the hippocampus. PERM (150 mg/kg and 300 mg/kg body weight/day, o.v.) increased lipoperoxidation and carbonylated proteins in a dose-dependent manner in the brain regions. The activities of antioxidant enzymes glutathione peroxidase, reductase, S-transferase, catalase, and superoxide dismutase showed an increase in all the different brain areas, with dose-dependent effects in the cerebellum. Cytokine profiles (IL-1β, IL-6 and TNF-α) increased in a dose-dependent manner in different brain tissues. Exposure to 150 mg/kg of permethrin induced degenerated and/or dead neurons in the rat hippocampus and induced mitochondrial uncoupling and reduction of oxidative phosphorylation and significantly decreased the respiratory parameters state 3-associated respiration in complex I and II. PERM exposure at low doses induces reactive oxygen species production and imbalance in the enzymatic antioxidant system, increases gene expression of pro-inflammatory interleukins, and could lead to cell damage mediated by mitochondrial functional impairment.

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Purpurogallin protects both ventricular myocytes and aortic endothelial cells of rats against oxyradical damage

Biochemistry and Cell Biology ◽

10.1139/o92-122 ◽

1992 ◽

Vol 70 (9) ◽

pp. 803-809 ◽

Cited By ~ 17

Author(s):

Tai-Wing Wu ◽

Jun Wu ◽

Doug Carey ◽

Ling-Hua Zeng

Keyword(s):

Endothelial Cells ◽

Xanthine Oxidase ◽

Ventricular Myocytes ◽

Cell Damage ◽

Dependent Manner ◽

Aortic Endothelial Cells ◽

Electron Microscopies ◽

First Time ◽

Dose Dependent ◽

Aortic Endothelial

Rat ventricular myocytes have been isolated and cultured by two separate procedures. Using phase-contrast and electron microscopies, we illustrate that (a) definitive cell damage is produced when myocytes are exposed to xanthine oxidase – hypoxanthine and (b) purpurogallin between 0.25 and 1.0 mM prolongs survival of both myocyte preparations in a dose-dependent manner. The cytoprotection produced by 1 mM purpurogallin exceeds that given by 2 mM each of ascorbate, Trolox, and mannitol, or 24 200 IU superoxide dismutase/L and (or) 92 000 IU catalase/L. Furthermore, we noted, for the first time, that purpurogallin markedly protects rat aortic endothelial cells, a key target of free radical generation and attack. In contrast, Trolox has a negligible effect here. Mechanistically, we showed that purpurogallin inhibits urate formation by xanthine oxidase more potently than allopurinol. Also, the compound diminishes formation of superoxide-reduced cytochrome c. Therefore, purpurogallin is a potent protector of ventricular myocytes and aortic endothelial cells, both of which are important cells in the cardiovascular system.Key words: purpurogallin, endothelial cells, myocytes.

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Antioxidant and Anti-Inflammatory Activities of Agrimonia pilosa Ledeb. Extract

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8571207 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Choon Young Kim ◽

Qi-Ming Yu ◽

Hyun-Joo Kong ◽

Joo-Yeon Lee ◽

Kyung-Mi Yang ◽

...

Keyword(s):

Cell Damage ◽

Reducing Power ◽

Total Phenolic ◽

Phytochemical Analysis ◽

Dependent Manner ◽

Inhibitory Effects ◽

Total Antioxidant ◽

Anti Inflammatory ◽

Species Production ◽

Dose Dependent

The purpose of this study is to investigate the effect of Agrimonia pilosa Ledeb. extract (APLE) on lipopolysaccharide- (LPS-) induced cell damage in hepatocytes with a focus on antioxidant and anti-inflammatory activities. Total antioxidant and anti-inflammatory activities of APLE itself were analyzed and phytochemical analysis was performed. Moreover, inhibitory effects of APLE on LPS-induced oxidative stress and inflammation were assessed in human HepG2 hepatocytes. APLE was found to exert α,α-diphenyl-β-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and nitrite scavenging activities and reducing power in a dose-dependent manner. The total phenolic and flavonoid contents of APLE were 44.30 ± 1.61 mg GAE/g and 29.65 ± 1.81 mg QE/g, respectively. HPLC analysis revealed that gallic acid is the major phenolic compound in APLE, followed by rutin, genistein, taxifolin, quercetin, luteolin, and apigenin, in descending order. Treatment of 100 and 200 μg/mL APLE significantly reduced LPS-stimulated intracellular reactive oxygen species production to the basal level without any cytotoxicity. Oppositely, APLE reversed LPS-suppressed expression of glutathione peroxidase gene and protein. Consistent with this result, APLE suppressed LPS-triggered expression of proinflammatory cytokine genes in a dose-dependent manner. These results reinforce the fact that the antioxidant and anti-inflammatory activity of APLE helps protect hepatocytes from LPS. Thus, APLE may be utilized as a bioactive ingredient in functional foods.

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Complement complex C5b-8 induces PGI2 formation in cultured endothelial cells

AJP Cell Physiology ◽

10.1152/ajpcell.1987.253.1.c13 ◽

1987 ◽

Vol 253 (1) ◽

pp. C13-C21 ◽

Cited By ~ 47

Author(s):

N. Suttorp ◽

W. Seeger ◽

S. Zinsky ◽

S. Bhakdi

Keyword(s):

Endothelial Cells ◽

Cell Damage ◽

Pulmonary Arterial ◽

Subsequent Activation ◽

Acid Pathway ◽

Complement Component C8 ◽

Arterial Endothelial Cells ◽

Dose Dependent ◽

Terminal Complement ◽

Passive Influx

The effects of the terminal complement sequence on prostacyclin (PGI2) generation in antibody-sensitized pulmonary arterial endothelial cells were examined. Whereas C5b-7 complement complexes induced no PGI2 formation, addition of purified complement component C8 resulted in a time- and dose-dependent burst of PGI2 release in the absence of overt cell damage. Formation of the complete terminal complement complex C5b-9 enhanced PGI2 release but was accompanied by cytolysis. Extracellular Ca2+ was required for C5b-8-dependent PGI2 formation. Three different blockers of physiological calcium channels failed to suppress the observed stimulatory effect. In contrast, W7 [N-(6-amino-hexyl)-5-chloro-1-naphthalene sulfonamide] and trifluoperazine, inhibitors of calmodulin activity, all reduced the C5b-8-dependent PGI2 generation. None of the inhibitors used impaired Ca2+ flux into the cells. One minute after addition of C8 to endothelial cells carrying C5b-7 complexes, a six- to seven-fold enhanced passive influx of 45Ca2+ into the cells was noted. An enhanced passive influx was also observed for 51Cr O4(2-), [3H] aminobutyric acid, and [3H]sucrose, but not for [3H]inulin and [3H]dextran. These data together suggest that complement C5b-8 complexes may serve as Ca2+ bypass gates in endothelial cells, the ensuing influx of Ca2+ leading to subsequent activation of the arachidonic acid pathway.

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Transcriptome Analysis Reveals a Signature Profile for Tick-Borne Flavivirus Persistence in HEK 293T Cells

mBio ◽

10.1128/mbio.00314-16 ◽

2016 ◽

Vol 7 (3) ◽

Cited By ~ 17

Author(s):

Luwanika Mlera ◽

Jennifer Lam ◽

Danielle K. Offerdahl ◽

Craig Martens ◽

Daniel Sturdevant ◽

...

Keyword(s):

Acute Phase ◽

Host Response ◽

Cell Damage ◽

Viral Persistence ◽

Dependent Manner ◽

Expression Levels ◽

Persistently Infected ◽

Infected Cells ◽

Cell Transcriptome ◽

Dose Dependent

ABSTRACT Tick-borne flaviviruses (TBFVs) cause febrile illnesses, which may progress to severe encephalitis and/or death in humans globally. Most people who recover from severe acute disease suffer from debilitating neurological sequelae, which may be due to viral persistence, infection-induced neurological cell damage, host response, or some combination of these. Acute TBFV infection of human embryonic kidney (HEK) 293T cells in vitro results in the death of >95% of infected cells by day 5. However, replacing cell growth medium allows surviving cells to repopulate and become persistently infected for extended periods of time. The mechanisms responsible for initiation and maintenance of viral persistence remain vague. We subjected the HEK 293T cell transcriptome to deep sequencing to identify genes differentially expressed during acute infection and persistent infection. A total of 451 genes showed unique significant differential expression levels in persistently infected cells relative to the acute phase of infection. Ingenuity Pathway Analysis results suggested that the expression of prosurvival oncogenes AKT2 and ERBB2 was upregulated in persistently infected cells, whereas proapoptotic genes, such as Bad and the beta interferon 1 (IFN-β1) gene, were downregulated. Genes encoding antiviral cytokines such as the CCL5, tumor necrosis factor alpha (TNF-α), and CXCL10 genes were upregulated during the acute phase, but the same genes were relatively quiescent in persistently infected cells. Exogenous induction of apoptosis demonstrated that persistently infected cells were resistant to apoptosis in a dose-dependent manner. In summary, the differential transcriptome profiles of acute-phase compared to persistently infected HEK 293T cells demonstrated an evasion of apoptosis, which may be critical for a chronic TBFV infection state. These results provide a basis for further study of the mechanisms of TBFV persistence. IMPORTANCE Tick-borne flaviviruses (TBFVs) cause life-threatening encephalitic disease in humans worldwide. Some people who recover from severe disease may suffer prolonged neurological symptoms due to either virus- or host response-induced cell damage or a combination of the two that are linked to viral persistence. By examining the genes that are significantly differentially expressed in acute TBFV infection versus persistent TBFV infection, we may be able to find the molecular basis of viral persistence. Here we used deep sequencing of the host cell transcriptome to discover that the expression levels of prosurvival genes were upregulated in persistently infected cells relative to acute TBFV infections whereas the expression levels of genes that promote programmed cell death were downregulated. In addition, persistently infected cells were also resistant to exogenous chemical induction of cell death, in a dose-dependent manner, compared to uninfected cells. Our results pave the way for further studies aimed at understanding the precise mechanisms of TBFV persistence.

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Protective Effects of the Extract of Juglans mandshurica Maxim on Endothelial Cell Damage

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.912-914.1965 ◽

2014 ◽

Vol 912-914 ◽

pp. 1965-1968

Author(s):

Wen He Zhu ◽

Wei Zhang ◽

Ying Xin Qin ◽

Nan Shen ◽

Li Jing Zhao ◽

...

Keyword(s):

Flow Cytometry ◽

Endothelial Cell ◽

Cell Damage ◽

Dependent Manner ◽

Protective Effects ◽

Juglans Mandshurica ◽

Endothelial Cell Damage ◽

In Vitro Methods ◽

Dose Dependent

Abstract: Objective: To investigate whether the extract of Juglans mandshurica maxim could inhibits the apoptosis induced by endogenous H2O2 on Endothelial Cell （EVC-304）in vitro. METHODS: Cultured EVC-304 cells were incubated with 10mUGOX or with 10mUGOX and different concentrations (25μg/ mL, 50μg/ mL, 100μg/ mL) of the extract of Juglans mandshurica maxim for 24h.The proliferation of EVC-304cells was detected by methyl thiazolyl tetrazolium (MTT) assay. The early apoptotic percent was measured by flow cytometry (FCM). RESULTS: MTT results showed that the inhibition proliferation of EVC-304 cells induced by endogenous H2O2 could be inhibited by the extract of Juglans mandshurica maxim in a dose -dependent manner. FCM assay indicated that, after treatment on EVC-304 cells with endogenous H2O2, the early apoptotic percent was increased, but the apoptosis rate was decreased significantly when the extract of Juglans mandshurica maxim added. CONCLUSION: the extract of Juglans mandshurica maxim protected significantly the cell damage and cell apoptosis induced by endogenous H2O2.

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Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite FormationIn Vitro

BioMed Research International ◽

10.1155/2015/925890 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Katharina Leitmeyer ◽

Andrea Glutz ◽

Vesna Radojevic ◽

Cristian Setz ◽

Nathan Huerzeler ◽

...

Keyword(s):

Hair Cell ◽

Hair Cells ◽

Cell Damage ◽

Spiral Ganglion ◽

Ganglion Neuron ◽

Spiral Ganglion Neuron ◽

Dependent Manner ◽

Auditory Hair Cells ◽

Ganglion Neurons ◽

Dose Dependent

Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR) by blocking the mTOR complex 1 (mTORC1). mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However, less is known about the mTOR pathway in the inner ear. First, we evaluated whether or not the two mTOR complexes (mTORC1 and mTORC2, resp.) are present in the mammalian cochlea. Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzedin vitro. Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells. Moreover, spiral ganglion neurite number and length of neurites were significantly decreased in all concentrations used compared to control in a dose dependent manner. Our data indicate that the mTOR may play a role in the survival of hair cells and modulates spiral ganglion neuronal outgrowth and neurite formation.

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