Selective cytotoxicity mechanisms and biodistribution of diamond nanoparticles on the skin cancer in C57 mouse

2021 ◽  
Author(s):  
Elham Moradi ◽  
Parvaneh Naserzadeh ◽  
Peiman Brouki Millan ◽  
Behnaz Ashtari
Keyword(s):  
Cell Death ◽  
Skin Cancer ◽  
Cytochrome C ◽  
Biological Activities ◽  
Cytochrome C Release ◽  
Diamond Nanoparticles ◽  
Test Conditions ◽  
Mda Content ◽  
Cell Death Signaling ◽  
High Cytotoxicity

Abstract The cytotoxicity of diamond nanoparticles (DNs) to various cell lines has been on focus by numerous scientists. The cellular toxicity system of DNs has not been fully understood or explained in skin cancer, at this point. This research was carried out to discover and reveal the potential impacts of DNs on the secluded brain, heart, liver, kidney, and skin in addition to evaluation of their cytotoxicity mechanism under test conditions. Their biological activities, for example cell viability, the level of reactive oxygen species (ROS), lipid peroxidation, cytochrome c release and Apoptosis/Necrosis were evaluated. Additionally, the bio-distribution of these nanomaterials in tissues was examined in the C57 mouse. Relying on the findings of the investigation, DNs were found to increase the ROS level, MDA content, release of cytochrome c, and cell death in skin significantly compared to other groups. In the C57 mouse, DNs were observed to have accumulated in skin tissue more intensively than they did in other organs. The present study presents for the the proof that DNs can completely induce cell death signaling in skin cancer without bringing about a high cytotoxicity in other tissues. Results suggest that DNs can be valuable in recognition of skin cancer.

scholarly journals Metformin inhibits mitochondrial permeability transition and cell death: a pharmacological in vitro study

2004 ◽  
Vol 382 (3) ◽  
pp. 877-884 ◽  
Author(s):  
Bruno GUIGAS ◽  
Dominique DETAILLE ◽  
Christiane CHAUVIN ◽  
Cécile BATANDIER ◽  
Frédéric De OLIVEIRA ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Cytochrome C Release ◽  
Intact Cells ◽  
Human Carcinoma ◽  
Butyl Hydroperoxide ◽  
Mitochondrial Permeability ◽  
New Findings

Metformin, a drug widely used in the treatment of Type II diabetes, has recently received attention owing to new findings regarding its mitochondrial and cellular effects. In the present study, the effects of metformin on respiration, complex 1 activity, mitochondrial permeability transition, cytochrome c release and cell death were investigated in cultured cells from a human carcinoma-derived cell line (KB cells). Metformin significantly decreased respiration both in intact cells and after permeabilization. This was due to a mild and specific inhibition of the respiratory chain complex 1. In addition, metformin prevented to a significant extent mitochondrial permeability transition both in permeabilized cells, as induced by calcium, and in intact cells, as induced by the glutathione-oxidizing agent t-butyl hydroperoxide. This effect was equivalent to that of cyclosporin A, the reference inhibitor. Finally, metformin impaired the t-butyl hydroperoxide-induced cell death, as judged by Trypan Blue exclusion, propidium iodide staining and cytochrome c release. We propose that metformin prevents the permeability transition-related commitment to cell death in relation to its mild inhibitory effect on complex 1, which is responsible for a decreased probability of mitochondrial permeability transition.

Abstract 371: Mitochondrial Antiviral Signaling (MAVS) Protects Cardiomyocytes Under Oxidative Stress by Interfering with Bax-Mediated Cell Death

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Toshitaka Yajima ◽  
Stanley Park ◽  
Hanbing Zhou ◽  
Michinari Nakamura ◽  
Mitsuyo Machida ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Membrane Potential ◽  
Cytochrome C ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Cytochrome C Release ◽  
Antiviral Signaling ◽  
Cell Death Pathway ◽  
The Impact

MAVS is a mitochondrial outer membrane protein that activates innate antiviral signaling by recognizing cytosolic viral RNAs and DNAs. While the discovery of MAVS is the first molecular evidence that links mitochondria to innate immune mechanisms, it is still unclear whether MAVS affects mitochondrial cell death as a member of caspase activation and recruitment domain (CARD)-containing proteins. We found that MAVS interacts with Bax through CARD by Yeast two-hybrid and a series of immunoprecipitation (IP) assay, which led us to hypothesize that MAVS functions not only in the innate antiviral mechanisms but also in the mitochondrial cell death pathway. Methods: 1) We examined molecular interaction between MAVS and Bax under oxidative stress by IP using isolated myocytes with H2O2 stimulation and the heart post ischemia-reperfusion (I/R). 2) We evaluated the effect of MAVS on mitochondrial membrane potential and apoptosis under H2O2 stimulation using isolated myocytes with adenoviral MAVS knockdown. 3) We investigated the impact of MAVS on %myocardial infarction (%MI) post I/R using cardiac-specific MAVS knockout (cKO) and transgenic (cTg) mice which we have originally generated. 4) We examined the effect of MAVS on recombinant Bax (rBax)-mediated cytochrome c release using isolated mitochondria from wild type (WT) and MAVS KO mice. Results: 1) The amount of Bax pulled down with MAVS was significantly increased in isolated myocytes with 0.2 mM H2O2 compared to those without stimulation (mean±SD; 1.808±0.14, n=5, p<0.001) and in the heart post I/R compared to sham (2.2±1.19, n=3, p=0.0081). 2) Myocytes with MAVS knockdown showed clear abnormalities in mitochondrial membrane potential and caspace-3 cleavage with 0.2 mM H2O2 compared to control cardiomyocytes. 3) MAVS cKO had significantly larger %MI than WT (81.9 ± 5.8% vs. 42.6 ± 13.6%, n=8, p=0.0008). In contrast, MAVS cTg had significantly smaller %MI that WT (30.0 ± 4.8% vs. 49.2 ± 4.8%, n=10, p=0.0113). 4) Mitochondria from MAVS KO exhibited cytochrome c release after incubation with 2.5 μ g of rBax while those from WT required 10 μ g of rBax. Conclusion: These results demonstrate that MAVS protects cardiomyocyte under oxidative stress by interfering with Bax-mediated cytochrome c release from mitochondria.

scholarly journals VANILLIN EXTRACTED FROM PROSO MILLET AND BARNYARD MILLET INDUCE APOPTOSIS IN HT-29 AND MCF-7 CELL LINE THROUGH MITOCHONDRIA MEDIATED PATHWAY

2017 ◽  
Vol 10 (12) ◽  
pp. 226 ◽  
Author(s):  
Deepa Priya Ramadoss ◽  
Nageswaran Sivalingam
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Barnyard Millet ◽  
Proso Millet ◽  
Ht 29 ◽  
Mcf 7

Objective: The main aim of the study was to investigate the bioactive compound vanillin extracted from proso millet (compound 1), and barnyard millet (compound 2) induces apoptotic cell death and whether it is mediated through mitochondrial pathway in HT-29 and MCF-7 cell line.Methods: The cells were treated with 250 μg/ml and 1000 μg/ml concentration of extracted vanillin for 48 hrs. Cytochrome c release and expression level of pro-apoptotic protein Bax and caspase-9 were detected by western blot analysis.Results: The results reveal that extracted compounds increased the release of cytochrome c and upregulating the expression of Bax and caspase-9 as concentration increases in a dose-dependent manner.Conclusion: The study suggests that the vanillin compound extracted from these millets induces apoptotic cell death through a mitochondria-dependent pathway.

scholarly journals Nuclear Translocation of Apoptosis-Inducing Factor after Focal Cerebral Ischemia

2004 ◽  
Vol 24 (4) ◽  
pp. 458-466 ◽  
Author(s):  
Nikolaus Plesnila ◽  
Changlian Zhu ◽  
Carsten Culmsee ◽  
Moritz Gröger ◽  
Michael A. Moskowitz ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Cytochrome C ◽  
Nuclear Translocation ◽  
Focal Cerebral Ischemia ◽  
Mitochondrial Protein ◽  
Neuronal Cell ◽  
Experimental Stroke ◽  
Cytochrome C Release ◽  
Apoptosis Inducing Factor

Signaling cascades associated with apoptosis contribute to cell death after focal cerebral ischemia. Cytochrome c release from mitochondria and the subsequent activation of caspases 9 and 3 are critical steps. Recently, a novel mitochondrial protein, apoptosis-inducing factor (AIF), has been implicated in caspase-independent programmed cell death following its translocation to the nucleus. We, therefore, addressed the question whether AIF also plays a role in cell death after focal cerebral ischemia. We detected AIF relocation from mitochondria to nucleus in primary cultured rat neurons 4 and 8 hours after 4 hours of oxygen/glucose deprivation. In ischemic mouse brain, AIF was detected within the nucleus 1 hour after reperfusion after 45 minutes occlusion of the middle cerebral artery. AIF translocation preceded cell death, occurred before or at the time when cytochrome c was released from mitochondria, and was evident within cells showing apoptosis-related DNA fragmentation. From these findings, we infer that AIF may be involved in neuronal cell death after focal cerebral ischemia and that caspase-independent signaling pathways downstream of mitochondria may play a role in apoptotic-like cell death after experimental stroke.

scholarly journals Hyperglycemia Enhances DNA Fragmentation after Transient Cerebral Ischemia

2001 ◽  
Vol 21 (5) ◽  
pp. 568-576 ◽  
Author(s):  
Ping-An Li ◽  
Ingrid Rasquinha ◽  
Qing Ping He ◽  
Bo K. Siesjö ◽  
Katalin Csiszár ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cell Death ◽  
Cytochrome C ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Cingulate Cortex ◽  
Tunel Staining ◽  
Dna Fragments ◽  
Cytochrome C Release ◽  
Klenow Polymerase

Previous histopathologic results have suggested that one mechanism whereby hyperglycemia (HG) leads to exaggerated ischemic damage involves fragmentation of DNA. DNA fragmentation in normoglycemia (NG) and HG rats subjected to 30 minutes of forebrain ischemia was studied by terminal deoxynucleotidyl transferase mediated DNA nick-labeling (TUNEL) staining, by pulse-field gel electrophoresis (PFGE), and by ligation-mediated polymerase chain reaction (LM-PCR). High molecular weight DNA fragments were detected by PFGE, whereas low molecular weight DNA fragments were detected using LM-PCR techniques. The LM-PCR procedure was performed on DNA from test samples with blunt (without Klenow polymerase) and 3′-recessed ends (with Klenow polymerase). In addition, cytochrome c release and caspase-3 activation were studied by immunocytochemistry. Results show that HG causes cytochrome c release, activates caspase-3, and exacerbates DNA fragments induced by ischemia. Thus, in HG rats, but not in control or NGs, TUNEL-stained cells were found in the cingulate cortex, neocortex, thalamus, and dorsolateral crest of the striatum, where neuronal death was observed by conventional histopathology, and where both cytosolic cytochrome c and active caspase-3 were detected by confocal microscopy. In the neocortex, both blunt-ended and stagger-ended fragments were detected in HG, but not in NG rats. Electron microscopy (EM) analysis was performed in the cingulate cortex, where numerous TUNEL-positive neurons were observed. Although DNA fragmentation was detected by TUNEL staining and electrophoresis techniques, EM analysis failed to indicate apoptotic cell death. It is concluded that HG triggers a cell death pathway and exacerbates DNA fragmentation induced by ischemia.

Hypoxia induces apoptosis via two independent pathways in Jurkat cells: differential regulation by glucose

2001 ◽  
Vol 281 (5) ◽  
pp. C1596-C1603 ◽  
Author(s):  
Ricky Malhotra ◽  
Zhiwu Lin ◽  
Claudius Vincenz ◽  
Frank C. Brosius
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Glucose Uptake ◽  
Molecular Mechanisms ◽  
Death Receptor ◽  
Jurkat Cells ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Extracellular Glucose ◽  
Uptake And Metabolism

Glucose uptake and metabolism inhibit hypoxia-induced apoptosis in a variety of cell types, but the underlying molecular mechanisms remain poorly understood. In the present study, we explore hypoxia-mediated cell death pathways in Jurkat cells in the presence and absence of extracellular glucose. In the absence of extracellular glucose, hypoxia caused cytochrome c release, caspase 3 and poly(ADP-ribose)polymerase cleavage, and DNA fragmentation; this apoptotic response was blocked by the caspase 9 inhibitor z-LEHD-FMK. The presence of extracellular glucose during hypoxia prevented cytochrome c release and activation of caspase 9 but did not prevent apoptosis in Jurkat cells. In these conditions, overexpression of the caspase 8 inhibitor v-FLIP prevented hypoxia-mediated cell death. Thus hypoxia can stimulate two apoptotic pathways in Jurkat cells, one dependent on cytochrome c release from mitochondria that is prevented by glucose uptake and metabolism, and the other independent of cytochrome c release and resulting from activation of the death receptor pathway, which is accelerated by glucose uptake and metabolism.

scholarly journals Inhibition of NGF deprivation–induced death by low oxygen involves suppression of BIMEL and activation of HIF-1

2005 ◽  
Vol 168 (6) ◽  
pp. 911-920 ◽  
Author(s):  
Liang Xie ◽  
Randall S. Johnson ◽  
Robert S. Freeman
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Protective Effect ◽  
Sympathetic Neurons ◽  
Hypoxia Inducible Factor ◽  
Trophic Factor ◽  
Low Oxygen ◽  
Cytochrome C Release ◽  
Targeted Deletion ◽  
Trophic Factor Deprivation

Changes in O2 tension can significantly impact cell survival, yet the mechanisms underlying these effects are not well understood. Here, we report that maintaining sympathetic neurons under low O2 inhibits apoptosis caused by NGF deprivation. Low O2 exposure blocked cytochrome c release after NGF withdrawal, in part by suppressing the up-regulation of BIMEL. Forced BIMEL expression removed the block to cytochrome c release but did not prevent protection by low O2. Exposing neurons to low O2 also activated hypoxia-inducible factor (HIF) and expression of a stabilized form of HIF-1α (HIF-1αPP→AG) inhibited cell death in normoxic, NGF-deprived cells. Targeted deletion of HIF-1α partially suppressed the protective effect of low O2, whereas deletion of HIF-1α combined with forced BIMEL expression completely reversed the ability of low O2 to inhibit cell death. These data suggest a new model for how O2 tension can influence apoptotic events that underlie trophic factor deprivation–induced cell death.

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