20 research outputs found
Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity
Manganese is a vital nutrient and is maintained at an optimal level (2.5ā5 mg/day) in human body. Chronic exposure to manganese
is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinsonās disease.
Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress
has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of
its correlation with the development of parkinsonism is poorly understood. Parkinsonās disease is characterized by the ļæ½-synuclein
aggregation in the form of Lewy bodies in neuronal cells. Recent fndings illustrate that manganese can cause overexpression of
ļæ½-synuclein. ļæ½-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis. ļæ½-Synuclein also causes
global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic diļ¬erence
may also have an inļ¬uence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinsonās disease.
Tis review presents the current state of fndings in relation to role of epigenetic mechanism in manganese induced neurotoxicity,
with a special emphasis on the development of Parkinsonās disease
Global DNA methylation profiling of manganese-exposed human neuroblastoma SH-SY5Y cells reveals epigenetic alterations in Parkinsonās disease-associated genes
Manganese (Mn) is an essential trace element required for optimal functioning of cellular biochemical pathways in the central nervous system. Elevated exposure to Mn through environmental and occupational exposure can cause neurotoxic effects resulting in manganism, a condition with clinical symptoms identical to idiopathic Parkinsonās disease. Epigenetics is now recognized as a biological mechanism involved in the etiology of various diseases. Here, we investigated the role of DNA methylation alterations induced by chronic Mn (100 ĀµM) exposure in human neuroblastoma (SH-SY5Y) cells in relevance to Parkinsonās disease. A combined analysis of DNA methylation and gene expression data for Parkinsonās disease-associated genes was carried out. Whole-genome bisulfite conversion and sequencing indicate epigenetic perturbation of key genes involved in biological processes associated with neuronal cell health. Integration of DNA methylation data with gene expression reveals epigenetic alterations to PINK1, PARK2 and TH genes that play critical roles in the onset of Parkinsonism. The present study suggests that Mn-induced alteration of DNA methylation of PINK1āPARK2 may influence mitochondrial function and promote Parkinsonism. Our findings provide a basis to further explore and validate the epigenetic basis of Mn-induced neurotoxicity
Manganese exposure: linking down-regulation of miRNA-7 and miRNA-433 with Ī±-synuclein overexpression and risk of idiopathic Parkinson's disease
Manganese is an essential trace element however elevated environmental and occupational exposure to this element has been correlated with neurotoxicity symptoms clinically identical to idiopathic Parkinson's disease. In the present study we chronically exposed human neuroblastoma SH-SY5Y cells to manganese (100 Ī¼M) and carried out expression profiling of miRNAs known to modulate neuronal differentiation and neurodegeneration. The miRNA PCR array results reveal alterations in expression levels of miRNAs, which have previously been associated with the regulation of synaptic transmission and apoptosis. The expressions of miR-7 and miR-433 significantly reduced upon manganese exposure. By in silico homology analysis we identified SNCA and FGF-20as targets of miR-7 and miR-433. We demonstrate an inverse correlation in expression levels where reduction in these two miRNAs causes increases in SNCA and FGF-20. Transient transfection of SH-SY5Y cells with miR-7 and miR-433 mimics resulted in down regulation of SNCA and FGF-20 mRNA levels. Our study is the first to uncover the potential link between manganese exposure, altered miRNA expression and parkinsonism: manganese exposure causes overexpression of SNCA and FGF-20 by diminishing miR-7 and miR-433 levels. These miRNAs may be considered critical for protection from manganese induced neurotoxic mechanism and hence as potential therapeutic targets
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Adsorption of an emerging contaminant (primidone) onto activated carbon: kinetic, equilibrium, thermodynamic, and optimization studies
The current study addresses the removal of an
emerging environmental contaminant (primidone) in
batch adsorption experiments using commercial-grade
powdered activated charcoal (PAC). The experiments
for the removal of primidone were performed to identify
the effect of various adsorption parameters. The secondorder
rate expression best represented the adsorption
kinetics data. The Freundlich isotherm equation was
best fitted to the experimental adsorption data at equilibriumfor
removal of primidone using PAC. The values
for change in entropy (ĪSo) were positive, which indicates
that the degree of freedomof the process increases.
The negative values of change in enthalpy (ĪHo) and
change in Gibbās free energy (ĪGo) indicate that the
physical adsorption is a dominant phenomenon, and the
process is feasible and spontaneous. The negative value
of ĪHo also represented the exothermicity of the adsorption
process. The Taguchi optimization technique
calculated the influence of variation of different process
parameters, viz., initial pH (pH0), PAC dosage (m),
initial adsorbate concentration (C0), solution temperature
(T), and process contact time (t), on the removal of
primidone by adsorption from aqueous solution. Each of
the above parameters was examined at three levels to
study their effects on the adsorptive uptake of primidone
using PAC (qe, mg gā1), and the optimum value necessary
to maximize qe was determined. The findings from
the ANOVA indicate that the PAC dose (m) is the most
notable parameter contributing 62.16% to qe and a
71.96% to the signal to noise (S/N) ratio data, respectively.
The confirmation experiments performed at the
optimum parameter condition validated the applicability
of the Taguchi design of experiments. The percent removal
and adsorptive uptake at the optimal condition
were 86.11% and 0.258 mg gā1, respectively
Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity
Manganese is a vital nutrient and is maintained at an optimal level (2.5ā5āmg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinsonās disease. Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of its correlation with the development of parkinsonism is poorly understood. Parkinsonās disease is characterized by the Ī±-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression of Ī±-synuclein. Ī±-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis. Ī±-Synuclein also causes global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic difference may also have an influence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinsonās disease. This review presents the current state of findings in relation to role of epigenetic mechanism in manganese induced neurotoxicity, with a special emphasis on the development of Parkinsonās disease
Personal and social issues involved in cancer development
Cancer is termed as a group of diseases and caused due to several genetic and environmental factors. Personal and social environments mostly decide the fate of cancer development in the community. With the advancement in cancer research, new therapeutic drugs and instruments have been developed to treat and cure cancer at an early stage of its development. However, less priority was given on the personal and social issues. Thus, the present review discusses the role of personal and social issues involved in the development of cancer
An integrated genomic and proteomic approach to identify signatures of endosulfan exposure in hepatocellular carcinoma cells
Present study reports the identi fication of genomic and proteomic signatures of endosulfan exposure in hepatocellular carcinoma cells (HepG2). HepG2 cells were exposed to sublethal concentration (15 Ī¼M) of endosulfan for
24 h. DNA microarray and MALDI āTOFāMS analyses revealed that endosulfan induced signi ficant alterations in
the expression level of genes and proteins involved in multiple cellular pathways (apoptosis, transcription, immune/in flammatory response, carbohydrate metabolism, etc.). Furthermore, downregulation of PHLDA gene,
upregulation of ACIN1 protein and caspase-3 activation in exposed cells indicated that endosulfan can trigger apoptotic cascade in hepatocellular carcinoma cells. In total 135 transcripts and 19 proteins were differentially
expressed. This study presents an integrated approach to identify the alteration of biological/cellular pathways
in HepG2 cells upon endosulfan exposur
Cellular alterations and modulation of protein expression in bitumen-challenged human osteoblast cells
Purpose
There are many arguments on the carcinogenic potential of bitumen extract. The mechanism of bitumen-induced damage is not well understood at the molecular level. Therefore, in the present study, cell-transforming and tumor-inducing potential of bitumen extract was studied using in vitro [human osteosarcoma (HOS) cells] and in vivo [nude and severe combined immunodeficiency (SCID) mice] models.
Methods
Gas chromatography/mass spectrometry (GC/MS) analysis was carried out to find out the existence of carcinogenic compounds in the bitumen extract. Cell transformation test, anchorage independence assay, karyotyping assay, tumorigenicity assay, and 2-DE analysis were used to find out the effect of bitumen using the in vitro and in vivo models.
Results
GC/MS analysis showed the existence of carcinogenic compounds in the bitumen extract. HOS cells were treated with different concentrations (25, 50, and 100 Ī¼l/ml) of bitumen extract. Compared to the parental HOS cells, bitumen transformants (HOS T1 and HOS T2) showed the characteristics of anchorage independency, chromosomal anomaly, and cellular transformation. Interestingly, bitumen transformants were not able to form tumor in nude/SCID mice. Proteomic analysis revealed the existence of 19 differentially expressed proteins involved in progression of cancer, angiogenesis, cell adhesion, etc.
Conclusions
Exposure of bitumen extract to HOS cells results in the cellular transformation similar to cancer cells and can modulate proteins involved in the progression of cancer. We state that the non-tumorogenic potential of bitumen transformant in nude/SCID mice can be attributed to the downregulation of galectin-1, chromodomain helicase DNA-binding protein 1-like gene, and membrane-associated guanylate kinase 2 protein
Carbonic anhydrase mediated carbon dioxide sequestration: Promises, challenges and future prospects
Anthropogenic activities have substantially increased the level of greenhouse gases (GHGs) in the atmosphere and are contributing significantly to the global warming. Carbon dioxide (CO2) is one of the major GHGs which plays a key role in the climate change. Various approaches and methodologies are under investigation to address CO2 capture and sequestration worldwide. Carbonic anhydrase (CA) mediated CO2 sequestration is one of the promising options. Therefore, the present review elaborates recent developments in CA, its immobilization and bioreactor methodologies towards CO2 sequestration using the CA enzyme. The promises and challenges associated with the efficient utilization of CA for CO2 sequestration and scale up from flask to labāscale bioreactor are critically discussed. Finally, the current review also recommends the possible future needs and directions to utilize CA for CO2 sequestration