Arsenate‐induced apoptosis in murine embryonic maxillary mesenchymal cells via mitochondrial‐mediated oxidative injury

Singh, Saurabh; Greene, Robert M.; Pisano, M. Michele

doi:10.1002/bdra.20623

Cited by 26 publications

(19 citation statements)

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“…No. E2261; Promega) expressing Renilla luciferase were transfected into freshly isolated murine embryonic maxillary mesenchymal (MEMM) cells, prepared essentially as described [33]. Transfection was performed in 2-ml media containing 3 × 10 5 cells using FuGENE6 Reagent (Cat.…”

Section: Methodsmentioning

confidence: 99%

Epigenetic Regulation of Sox4 during Palate Development

et al. 2013

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Aim Identification of genes that contribute to secondary palate development provide a better understanding of the etiology of palatal clefts. Gene-expression profiling of the murine palate from gestational days 12–14 (GD12–14), a critical period in palate development, identified Sox4 as a differentially expressed gene. In this study, we have examined if the differential expression of Sox4 in the palate is due to changes in DNA methylation. Materials & methods In situ hybridization analysis was used to localize the expression of Sox4 in the developing murine secondary palate. CpG methylation profiling of a 1.8-kb upstream region of Sox4 in the secondary palate from GD12–14 and transfection analysis in murine embryonic maxillary mesenchymal cells using Sox4 deletion, mutant and in vitro methylated plasmid constructs were used to identify critical CpG residues regulating Sox4 expression in the palate. Results Spatiotemporal analysis revealed that Sox4 is expressed in the medial edge epithelium and presumptive rugae-forming regions of the palate from GD12 to GD13. Following palatal shelf fusion on GD14, Sox4 was expressed exclusively in the epithelia of the palatal rugae, structures that serve as signaling centers for the anteroposterior extension of the palate, and that are thought to serve as neural stem cell niches. Methylation of a 1.8-kb region upstream of Sox4, containing the putative promoter, completely eliminated promoter activity. CpG methylation profiling of the 1.8-kb region identified a CpG-poor region (DMR4) that exhibited significant differential methylation during palate development, consistent with changes in Sox4 mRNA expression. Changes in the methylation of DMR4 were attributed primarily to CpGs 83 and 85. Conclusion Our studies indicate that Sox4 is an epigenetically regulated gene that likely integrates multiple signaling systems for mediating palatal fusion, palatal extension and/or the maintenance of the neural stem cell niche in the rugae.

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Section: Methodsmentioning

confidence: 99%

Epigenetic Regulation of Sox4 during Palate Development

et al. 2013

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“…This reducing environment is preserved by enzymes that maintain the reduced state through a constant input of metabolic energy [5]. Disturbances in this normal redox state can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids and DNA [6]. In humans, oxidative stress is involved in many diseases, such as atherosclerosis, Parkinson's disease, heart failure, myocardial infarction, Alzheimer's disease, fragile X syndrome and chronic fatigue syndrome (CFS), but short-term oxidative stress may also be important in prevention of ageing by induction of a process called mitohormesis [7].…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Status and Oxidative Stress in Patients with Chronic ITP

et al. 2013

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The aim of this study was to establish the antioxidant status and oxidative stress in adult patients with chronic idiopathic thrombocytopenic purpura (ITP). Eighty-four patients diagnosed with chronic ITP were studied. Fiftyeight age-matched healthy subjects were selected as controls. Serum nitrogen monoxide ( NO), oxidized glutathione (GSSG), malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), hydrogen peroxide enzyme (CAT), glutathione peroxidase (GSH-Px), glutathione (GSH) were evaluated by enzyme-linked immunosorbent assay (ELISA). It was found that serum SOD, CAT, GSH-Px, GSH, TAS levels were significantly lower in patients with chronic ITP than controls (all P < 0.05), while serum NO, GSSG, MDA, TOS values were significantly higher (P < 0.05). The number of platelet showed a negative correlation with NO, GSSG, MDA, TOS, respectively,while platelet number showed a positive correlation with SOD, CAT, GSH-Px, GSH, TAS. These findings suggested that oxidants were increased and antioxidants were decreased in patients with chronic ITP, these may be prominent factors in destructing the platelet membrane. The scavenging of oxygen radical provides a theoretical basis for the treatment of ITP patients.

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“…A number of studies showed that As exposure could induce apoptosis in a variety of cells 32−34) . Singh et al (2010) demonstrated that exposure to arsenate induced apoptosis in the murine embryonic maxillary mesenchymal (MEMM) cells 34) . It was reported that chronic exposure to As increased apoptosis in the neuronal cells of the brain 15) .…”

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confidence: 99%

“…Yadav et al (2010) reported that As exposure induced apoptosis in bone marrow mesenchymal stem cells, downregulation of Bcl-2 mRNA expression and upregulation of Bax mRNA expression 37) . Singh et al (2010) demonstrated that exposure to arsenate increased the Bax protein level and decreased the Bcl-2 protein level in murine embryonic maxillary mesenchymal cells 34) . In the present study, the expression of Bax and Bcl-2 in the hippocampus was also analyzed by real-time PCR and Western blotting.…”

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confidence: 99%

Subchronic exposure to arsenic induces apoptosis in the hippocampus of the mouse brains through the Bcl‐2/Bax pathway

Wang

Bai

Guan

et al. 2015

Journal of Occupational Health

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were found in the hippocampus of As-exposed mice. The expressions of the Bcl-2 gene and its protein in the hippocampus of As-exposed mice were significantly lower than those in the control group (p<0.05). However, the expressions of the Bax gene and its protein, and the expression ratio of Bax/Bcl-2 in the hippocampus were significantly higher in the groups exposed to As than in the control group (p<0.05). Moreover, the activity of caspase-3 in the hippocampus of mice exposed to As was higher than that in the control (p<0.05). Conclusions:These results indicate that subchronic exposure to As induces apoptosis in the hippocampus of mice by disturbing normal Bax/Bcl-2 regulatory pathways. Meanwhile, it is suggested that the induced apoptosis in the hippocampus may be at least partly responsible for As-induced neurotoxicity. (J Occup Health 2015; 57: 212-221) Key words: Apoptosis, Arsenic trioxide, Bax, Bcl-2, Hippocampus, Neurotoxicity Arsenic (As), a naturally occurring toxic metalloid found in both inorganic and organic forms, is ubiquitous in the environment and contaminates water as a result of geological and industrial pollution 1) . Moreover, some kinds of arsenide, such as arsenic trioxide (As 2 O 3 ), are also widely used for the treatment of malignant tumors 2) . In As-contaminated areas, the As concentration in drinking water or groundwater ranges from 0.25 to 2.1 ppm and even reaches >3.0 ppm in some severely contaminated areas 3−5) . Exposure to As has been associated with increasing incidences of various chronic diseases, including peripheral vascular disease, cardiovascular disease, diabetes mellitus, and various cancers 6) . As is also a potent neurotoxicant, and subchronic or chronic As exposure causes severe nervous system Abstract: Subchronic exposure to arsenic induces apoptosis in the hippocampus of the mouse brains through the Bcl-2/Bax pathway: Yachen WANG, et al. Department of Occupational and EnvironmentalHealth, Dalian Medical University, P.R. ChinaObjectives: The aim of this study was to identify whether arsenic (As) exposure could induce hippocampal neural apoptosis in vivo. Methods: Sixty-four mice were randomly divided into 4 groups of 16 each. Group 1 orally received drinking water alone as a control. Groups 2−4 were given arsenic trioxide (As 2 O 3 ) orally at the doses of 1 ppm, 2 ppm and 4 ppm, respectively. All the treatments continued for 60 days. Morphological changes in the hippocampus were observed by HE staining. Apoptosis in the hippocampus was examined by TUNEL assay and transmission electron microscopy. The expression levels of Bcl-2 and Bax genes and their proteins in the hippocampus were determined by realtime PCR and Western blotting. The activity of caspase-3 was determined by spectrophotometry. Results: Abnormal histopathological changes and apoptosis

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Arsenate‐induced apoptosis in murine embryonic maxillary mesenchymal cells via mitochondrial‐mediated oxidative injury

Cited by 26 publications

References 50 publications

Epigenetic Regulation of Sox4 during Palate Development

Epigenetic Regulation of Sox4 during Palate Development

Antioxidant Status and Oxidative Stress in Patients with Chronic ITP

Subchronic exposure to arsenic induces apoptosis in the hippocampus of the mouse brains through the Bcl‐2/Bax pathway

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