Saravanadevi Sivanesan

Biodegradation and detoxification of chloronitroaromatic pollutant by Cupriavidus

Current study reports isolation of Cupriavidus strain a3 which can utilize 2-chloro-4-nitrophenol (C4NP) as sole source of carbon and nitrogen, leading to its detoxification. Degradation process was initiated by release of nitrite ion resulting in the formation of 2-chlorohydroquinone as intermediate. The nitrite releasing activity was also evident in the cell free protein extract. Different parameters for 2C4NP biodegradation were optimized. The degradation pattern followed Haldane substrate inhibition model with maximum specific degradation rate (qmax) of 0.13/h, half saturation constant (Ks) of 0.05mM, and 2C4NP inhibition constant (Ki) of 0.64mM. The isolate was successfully applied to remediation of 2C4NP-contaminated soil in microcosm study. 2-Dimensional protein electrophoresis analysis showed that growth of the isolate in the presence of 2C4NP resulted in modification of membrane permeability and induction of signal transduction protein. In our knowledge, this is the first study reporting degradation and detoxification of 2C4NP by Cupriavidus.

Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity

Manganese is a vital nutrient and is maintained at an optimal level (2.5–5 mg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinsons 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. Parkinsons disease is characterized by the α-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression of α-synuclein. α-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis. α-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 Parkinsons 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 Parkinsons disease.

Noncoding RNAs: Possible Players in the Development of Fluorosis

Fluorosis is caused by excess of fluoride intake over a long period of time. Aberrant change in the Runt-related transcription factor 2 (RUNX2) mediated signaling cascade is one of the decisive steps during the pathogenesis of fluorosis. Up to date, role of fluoride on the epigenetic alterations is not studied. In the present study, global expression profiling of short noncoding RNAs, in particular miRNAs and snoRNAs, was carried out in sodium fluoride (NaF) treated human osteosarcoma (HOS) cells to understand their possible role in the development of fluorosis. qPCR and in silico hybridization revealed that miR-124 and miR-155 can be directly involved in the transcriptional regulation of Runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor κ-B ligand (RANKL) genes. Compared to control, C/D box analysis revealed marked elevation in the number of UG dinucleotides and D-box sequences in NaF exposed HOS cells. Herein, we report miR-124 and miR-155 as the new possible players involved in the development of fluorosis. We show that the alterations in UG dinucleotides and D-box sequences of snoRNAs could be due to NaF exposure.

The health burden and economic costs averted by ambient PM 2.5 pollution reductions in Nagpur, India

National estimates of the health and economic burdens of exposure to ambient fine particulate matter (PM2.5) in India reveal substantial impacts. This information, often lacking at the local level, can justify and drive mitigation interventions. Here, we assess the health and economic gains resulting from attainment of WHO guidelines for PM2.5 concentrations - including interim target 2 (IT-2), interim target 3 (IT-3), and the WHO air quality guideline (AQG) - in Nagpur district to inform policy decision making for mitigation. We conducted a detailed assessment of concentrations of PM2.5 in 9 areas, covering urban, peri-urban and rural environments, from February 2013 to June 2014. We used a combination of hazard and survival analyses based on the life table method to calculate attributed annual number of premature deaths and disability-adjusted life years (DALYs) for five health outcomes linked to PM2.5 exposure: acute lower respiratory infection for children <5years, ischemic heart disease, chronic obstructive pulmonary disease, stroke and lung cancer in adults ≥25years. We used GBD 2013 data on deaths and DALYs for these diseases. We calculated averted deaths, DALYs and economic loss resulting from planned reductions in average PM2.5 concentration from current level to IT-2, IT-3 and AQG by the years 2023, 2033 and 2043, respectively. The economic cost for premature mortality was estimated as the product of attributed deaths and value of statistical life for India, while morbidity was assumed to be 10% of the mortality cost. The annual average PM2.5 concentration in Nagpur district is 34±17μgm-3 and results in 3.3 (95% confidence interval [CI]: 2.6, 4.2) thousand premature deaths and 91 (95% CI: 68, 116) thousand DALYs in 2013 with economic loss of USD 2.2 (95% CI: 1.7, 2.8) billion in that year. It is estimated that interventions that achieve IT-2, IT-3 and AQG by 2023, 2033 and 2043, would avert, respectively, 15, 30 and 36%, of the attributed health and economic loss in those years, translating into an impressively large health and economic gain. To achieve this, we recommend an exposure-integrated source reduction approach.

Stress response of Pseudomonas species to silver nanoparticles at the molecular level

In recent years, silver nanoparticles (AgNPs) have been shown to possess broad antibacterial activity. The present study investigated the cytotoxicity of AgNPs to a common soil bacterium, Pseudomonas sp. The molecular mechanism involved in its stress response to AgNPs was also studied. The minimum inhibitory concentration (MIC) of AgNPs was found to be 0.2 mg/L. At a sublethal concentration of 0.1 mg/L AgNPs, the protein expression profile of Pseudomonas showed overexpression of stress proteins such as ribosomal proteins S2 and L9, alkyl hydroperoxide reductase/thiol-specific antioxidant (AhpC/TSA) family protein, and keto-hydroxyglutarate aldolase (KHGA). The upregulation of these proteins was further confirmed by quantitative polymerase chain reaction. The results showed increased expression of ribosomal protein S2, KHGA, AhpC/TSA, and ribosomal protein L9 by 1.09-, 3.41-, 1.52-, and 1.56-fold, respectively (p < 0.05), after AgNP exposure compared with control. The present study clearly demonstrates that AgNPs are toxic to soil bacteria and induce oxidative and metabolic stress.

Correlation of melanophore index with a battery of functional genomic stress indicators for measurement of environmental stress in aquatic ecosystem

The correlation of primary stress indicator; melanophore index (MI) with set of genomic stress indicators is important for a better understanding of the cellular stress pathway induced by xenobiotics in aquatic species. This study presents a correlation between melanophore index (MI) and genomic stress indicators in Oreochromis mossambicus treated with lead nitrate, phenol and hexachlorocyclohexane (HCH). O. mossambicus was exposed to sub-lethal concentrations of the different LC50 values (96 h) of the tested chemicals at varying exposure periods and the response via genomic stress indicators and scale melanophores were assessed in accordance with standard protocols. Melanophore index decreased significantly (p<0.01) in a time dependent pattern to the tested chemicals. Gene expression showed significant time dependent increase in the expression of heat shock proteins (HSP70 and HSP60). Vitellogenin (Vtg) expression insignificantly altered. Significant increase in the expression of melanin concentrating hormone (MCH) was observed in response to hexachlorocyclohexane (HCH) in the treated fish. The findings demonstrated an inverse relationship between melanophore index and the set of genomic stress indicators.

Cytochrome P450 BM3 of Bacillus megaterium - a possible endosulfan biotransforming gene.

Computing chemistry was applied to understand biotransformation mechanism of an organochlorine pesticide, endosulfan. The stereo specific metabolic activity of human CYP-2B6 (cytochrome P450) on endosulfan has been well demonstrated. Sequence and structural similarity search revealed that the bacterium Bacillus megaterium encodes CYP-BM3, which is similar to CYP-2B6. The functional similarity was studied at organism level by batch-scale studies and it was proved that B. megaterium could metabolize endosulfan to endosulfan sulfate, as CYP-2B6 does in human system. The gene expression analyses also confirmed the possible role of CYP-BM3 in endosulfan metabolism. Thus, our results show that the protein structure based in-silico approach can help us to understand and identify microbes for remediation strategy development. To the best of our knowledge this is the first report which has extrapolated the bacterial gene for endosulfan biotransformation through in silico prediction approach for metabolic gene identification.

Integrative genomic and proteomic profiling of human neuroblastoma SH-SY5Y cells reveals signatures of endosulfan exposure

Endosulfan, an organochlorine pesticide, is known to induce multiple disorders/abnormalities including neuro-degenerative disorders in many animal species. However, the molecular mechanism of endosulfan induced neuronal alterations is still not well understood. In the present study, the effect of sub-lethal concentration of endosulfan (3 μM) on human neuroblastoma cells (SH-SY5Y) was investigated using genomic and proteomic approaches. Microarray and 2D-PAGE followed by MALDI-TOF-MS analysis revealed differential expression of 831 transcripts and 16 proteins in exposed cells. A gene ontology enrichment analysis revealed that the differentially expressed genes and proteins were involved in variety of cellular events such as neuronal developmental pathway, immune response, cell differentiation, apoptosis, transmission of nerve impulse, axonogenesis, etc. The present study attempted to explore the possible molecular mechanism of endosulfan induced neuronal alterations in SH-SY5Y cells using an integrated genomic and proteomic approach. Based on the gene and protein profile possible mechanisms underlying endosulfan neurotoxicity were predicted.

Manganese exposure: Linking down-regulation of miRNA-7 and miRNA-433 with α-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 Parkinsons disease. In the present study we chronically exposed human neuroblastoma SH-SY5Y cells to manganese (100μM) 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.

The burden of disease attributable to ambient PM2.5-bound PAHs exposure in Nagpur, India

Exposure to PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) can elicit several types of cancer and non-cancer effects. Previous studies reported substantial burdens of PAH-induced lung cancer, but the burdens of other cancer types and non-cancer effects remain unknown. Thus, we estimate the cancer and non-cancer burden of disease, in disability-adjusted life years (DALYs), attributable to ambient PM2.5-bound PAHs exposure in Nagpur district, India, using risk-based approach. We measured thirteen PAHs in airborne PM2.5 sampled from nine sites covering urban, peri-urban and rural areas, from February 2013 to June 2014. We converted PAHs concentrations to benzo[a]pyrene equivalence (B[a]Peq) for cancer and non-cancer effects using relative potency factors, and relative toxicity factors derived from quantitative structure-activity relationships, respectively. We calculated time-weighted exposure to B[a]Peq, averaged over 30 years, and adjusted for early-life susceptibility to cancer. We estimated the DALYs/year using B[a]Peq exposure levels, published toxicity data, and severity of the diseases from Global Burden of Disease 2016 database. The annual average concentration of total PM2.5-bound PAHs was 458 ± 246 ng/m3 and resulted in 49,500 DALYs/year (0.011 DALYs/person/year). The PAH-related DALYs followed this order: developmental (mostly cardiovascular) impairments (55.1%) > cancer (26.5%) or lung cancer (23.1%) > immunological impairments (18.0%) > reproductive abnormalities (0.4%).