Dev S.,Jawaharlal Nehru UniversityNew Delhi |
Kumari S.,Jawaharlal Nehru UniversityNew Delhi |
Singh N.,Case Western Reserve University |
Kumar Bal S.,Jawaharlal Nehru UniversityNew Delhi |
And 2 more authors.
Free Radical Biology and Medicine | Year: 2015
Abstract Iron accumulation and oxidative stress are associated with neurodegenerative disease. Labile iron is known to catalyze free radical generation and subsequent neuronal damage, whereas the role of oxidative stress in neuronal iron accumulation is less well understood. Here, we examined the effect of hydrogen peroxide (H2O2) treatment on cellular iron-uptake, -storage, and -release proteins in the neuroblastoma cell line SH-SY5Y. We found no detectable change in the iron-uptake proteins transferrin receptor-1 and divalent metal ion transporter. In contrast, H2O2 treatment resulted in significant degradation of the iron-exporter ferroportin (Fpn). A decrease in Fpn is expected to increase the labile iron pool (LIP), reducing the iron-regulatory protein (IRP)-iron-responsive element interaction and increasing the expression of ferritin-H (Ft-H) for iron storage. Instead, we detected IRP1 activation, presumably due to oxidative stress, and a decrease in Ft-H translation. A reduction in Ft-H mRNA was also observed, probably dependent on an antioxidant-response element present in the Ft-H enhancer. The decrease in Fpn and Ft-H upon H2O2 treatment led to a time-dependent increase in the cellular LIP. Our study reveals a complex regulation of neuronal iron-release and iron-storage components in response to H2O2 that may explain iron accumulation detected in neurodegenerative diseases associated with oxidative stress. © 2015 Elsevier Inc.
Kumar M.,Tezpur University |
Kumar M.,University of Nebraska - Lincoln |
Das N.,Tezpur University |
Goswami R.,Tezpur University |
And 3 more authors.
Chemosphere | Year: 2016
The present work is an attempt to study As and F+ coevality using laboratory based assays which couples fractionation and batch dissolution experiments. Sequential extraction procedure (SEP) resulting into five “operationally defined phases”, was performed on sediment and soil samples collected from the Brahmaputra flood plains, Assam, India. High correlation between the Fe (hydr)oxide fraction and total As content of the soil/sediment sample indicates the involvement of Fe (hydr)oxides as the principal source of As. F− being an anion has high potential to be sorbed onto positively charged surfaces. Findings of the SEP were used to design the batch desorption experiments by controlling the Fe (hydr)oxide content of the soil/sediment. Desorption of As and F− was observed under acidic, neutral and alkaline pH from untreated and Fe (hydr)oxide removed samples. Highest amount of As and F− were found to be released from untreated samples under alkaline pH, while the amount leached from samples with no Fe (hydr)oxide was low. The study showed that the Fe (hydr)oxide fraction commonly found in the soils and sediments, had high affinity for negatively charged species like F− oxyanions of As, AsO4 3− (arsenate) and AsO3 3− (arsenite). Fe (hydr)oxide fraction was found to play the major role in co-evolution of As and F−. Two sorption coefficients were proposed based on easily leachable fraction and As present in the groundwater of sampling location for understanding of contamination vulnerability from the leaching. © 2016 Elsevier Ltd
Das M.T.,Jawaharlal Nehru UniversityNew Delhi |
Singh M.K.,Jawaharlal Nehru UniversityNew Delhi |
Thakur I.S.,Jawaharlal Nehru UniversityNew Delhi
Indian Journal of Experimental Biology | Year: 2014
Wide spread use of Di-(2-ethylhexyl) phthalate (DEHP) has made it a ubiquitous contaminant in today’s environment, responsible for possible carcinogenic and endocrine disrupting effects. In the present investigation an integrative toxicoproteomic approach was made to study the estrogenic potential of DEHP. In vitro experiments carried out with DEHP (0.1-100 μM) induced proliferations (E-screen assay) in human estrogen receptors-α (ERα) positive MCF-7 and ERα negative MDA-MB-231 breast cancer cells irrespective of their ERα status. Further, DEHP suppressed tamoxifen (a potent anti-breast cancer drug) induced apoptosis in both cell types as shown by flowcytometric cell cycle analysis. Label-free quantitative proteomics analysis of the cell secretome of both the cell lines indicated a wide array of stress related, structural and receptor binding proteins that were affected due to DEHP exposure. The secretome of DEHP treated MCF-7 cells revealed the down regulation of lactotransferrin, an ERα responsive iron transport protein. The results indicated that toxicological effects of DEHP did not follow an ERα signaling pathway. However, the differential effects in MCF-7 and MDA-MB-231 cell lines indicate that ERα might have an indirect modulating effect on DEHP induced toxicity. ©, National Institute of Science Communication. All rights reserved.
Kumar S.,Jawaharlal Nehru UniversityNew Delhi |
Tiku A.B.,Jawaharlal Nehru UniversityNew Delhi
Food and Agricultural Immunology | Year: 2016
Plant polysaccharides have been reported to stimulate growth, differentiation and proliferation of hematopoietic progenitor and stem cells to protect against the deleterious effects of radiations. This study evaluated the radioprotective potential of acemannan, a major polysaccharide component of aloe vera gel. Treatment of mice with 50 mg/kg body weight of acemannan by oral gavage for 7 days was able to protect against the radiation-induced mortality. Seven-day pretreatment or post-treatment of mice with acemannan resulted in the increase in median survival by 60 and 20%, respectively. The decrease in mortality can be attributed to the induction of hematopoiesis (peripheral lymphocytes counts, spleen cellularity, spleen index) and the upregulation of cytokines like TNF-α and IL-1 by acemannan in irradiated mice. Data indicate that acemannan has the ability to protect mice against radiation-induced mortality by immunomodulation and can be developed as a radiation damage mitigation agent. © 2015 Taylor & Francis.
Singh S.L.,Jawaharlal Nehru UniversityNew Delhi |
Rai R.C.,Jawaharlal Nehru UniversityNew Delhi |
Rai R.C.,Research Scientist |
Komath S.S.,Jawaharlal Nehru UniversityNew Delhi
Yeast | Year: 2016
CaGpi14 is the catalytic subunit of the first mannosyltransferase that is involved in the glycosylphosphatidylinositol (GPI) biosynthetic pathway in Candida albicans. We show that CaGPI14 is able to rescue a conditionally lethal gpi14 mutant of Saccharomyces cerevisiae, unlike its mammalian homologue. The depletion of this enzyme in C. albicans leads to severe growth defects, besides causing deficiencies in GPI anchor levels. In addition, CaGpi14 depletion results in cell wall defects and upregulation of the cell wall integrity response pathway. This in turn appears to trigger the osmotic-stress dependent activation of the HOG1 pathway and an upregulation of HOG1 as well as its downstream target, SKO1, a known suppressor of expression of hyphae-specific genes. Consistent with this, mutants of CaGPI14 are unable to undergo hyphal transformations in different hyphae-inducing media, under conditions that produce abundant hyphae in the wild-type cells. Hyphal defects in the CaGPI14 mutants could not be attributed either to reduced protein kinase C activation or to defective Ras signalling in these cells but appeared to be driven by perturbations in the HOG1 pathway. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Kumar B.,Jawaharlal Nehru UniversityNew Delhi |
Iqbal M.A.,Jawaharlal Nehru UniversityNew Delhi |
Singh R.K.,Jawaharlal Nehru UniversityNew Delhi |
Bamezai R.N.K.,Jawaharlal Nehru UniversityNew Delhi
Biochimie | Year: 2015
Abstract Resveratrol has been shown to exhibit its anti-cancer effect through a variety of mechanisms. Here, TIGAR (TP53-Induced Glycolysis and Apoptosis Regulator) was identified as an important target of resveratrol for exhibiting ROS-dependent-consequences on apoptosis and autophagy. Resveratrol treatment decreased TIGAR protein irrespective of cell line used. Down-regulated TIGAR protein triggered a drop in reduced-glutathione levels which resulted in sustained ROS, responsible for apoptosis and autophagy. Over-expression and silencing experiments demonstrated the importance of TIGAR in affecting the ROS-dependent anti-cancer effects of resveratrol. Resveratrol treated cells exhibited autophagy to escape apoptosis, however, chloroquine treatment along with resveratrol, blocked protective autophagy and facilitated apoptosis. Collectively, results unravel the effects of resveratrol on TIGAR in mediating its ROS dependent influence and suggest a better combination therapy of resveratrol and chloroquine for probable cancer treatment. © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM).
Chatrath S.,National Institute of Immunology |
Gupta V.K.,National Institute of Immunology |
Gupta V.K.,University of Minnesota |
Dixit A.,Jawaharlal Nehru UniversityNew Delhi |
Garg L.C.,National Institute of Immunology
Microbes and Infection | Year: 2016
The success of Mycobacterium tuberculosis as a pathogen relies on its ability to survive inside macrophages and evade host immune mechanisms. M. tuberculosis employs multiple strategies to confer resistance against immune system including inhibition of phago-lysosomal fusion, modulation of cytokine responses and granuloma formation. PE_PGRS proteins, uniquely present in pathogenic mycobacteria, are cell surface molecules that are suggested to interact with host cells. PE_PGRS proteins have also been implicated in its pathogenesis. In the present study, immuno-regulatory property of Rv1651c-encoded PE_PGRS30 protein was explored. Infection of PMA-differentiated human THP-1 macrophages with Mycobacterium smegmatis harbouring pVV1651c resulted in reduced production of IL-12, TNF-α and IL-6, as compared to infection with M. smegmatis harbouring the control plasmid pVV16. No differential effect was observed on bacterial persistence inside macrophages or on macrophage mortality upon infection with the two recombinant strains. Infection of THP-1 macrophages with recombinant M. smegmatis expressing deletion variants of PE_PGRS30 indicated that anti-inflammatory function of the protein is possessed by its PGRS and PE domains while the C-terminal domain, when expressed alone, displayed antagonistic effect in terms of TNF-α secretion. These results suggest that PE_PGRS30 interferes with macrophage immune functions important for activation of adaptive T-cell responses. © 2016 Institut Pasteur
Pathak J.,Jawaharlal Nehru UniversityNew Delhi |
Rawat K.,Jawaharlal Nehru UniversityNew Delhi |
Rawat K.,Inter University Accelerator Center |
Bohidar H.B.,Jawaharlal Nehru UniversityNew Delhi
RSC Advances | Year: 2015
An understanding of the interactions between gelatin B (GB) and β-lacto-globulin (β-Lg) mainly arising from surface selective patch binding occurring at their common pI (≈5.0 ± 0.5) in the absence of added salt. Heterogeneous surface charge distribution on β-Lg facilitated such interaction at different mixing ratio ([GB]: [β-Lg] = r) and the GB-β-Lg complexes carried distinctive surface charge (seen through their zeta potential, ζ). For r < 1 : 1 (partial charge neutralization, ζ ≈ 0) a turbid solution was formed which gives the indication of formation of intermolecular soluble complexes. For r > 1 : 1 (overcharged regime, ζ > 0) the dispersion remained transparent and homogeneous which gives no phase separation, but the dispersion formed a gel on waiting. The overcharged gels were homogeneous, more rigid and higher melting temperature in comparison to coacervate. In the coacervate phase, the intensity of the scattered light Is, and its time-correlation function [g2(t) - 1] did not evolve with time. In contrast, the gel phase displayed considerable change with aging time tw. For gels, as tw → ∞ the system moved from an ergodic to non-ergodic state. At tw = 0, the correlation function exhibited one relaxation mode due to the system residing deeply inside the ergodic phase and purely mirroring Brownian dynamics. After a characteristic waiting time, tw an additional mode (slow relaxation) appeared which was attributed to inter-chain interaction induced reorganization of entanglements. This characteristic time was the time required for the system to get dynamically arrested, similar observation was made from rheology measurements too. A comprehensive phase diagram depicting the stability of the dispersion in various charged soft matter states of the complex under various temperature conditions was established. This journal is © The Royal Society of Chemistry.
Sharma A.,Jawaharlal Nehru UniversityNew Delhi |
Baral D.,Jawaharlal Nehru UniversityNew Delhi |
Bohidar H.B.,Jawaharlal Nehru UniversityNew Delhi |
Solanki P.R.,Jawaharlal Nehru UniversityNew Delhi
Chemico-Biological Interactions | Year: 2015
Abstract A label free impedimetric immunosensor has been fabricated using protein bovine serum albumin (BSA) and monoclonal antibodies against Vibrio cholerae (Ab) functionalized oxalic acid (OA) capped iron oxide (Fe3O4) nanorods for V. cholerae detection. The structural and morphological studies of Fe3O4 and OA-Fe3O4, were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and dynamic light scattering (DLS) techniques. The average crystalline size of Fe3O4, OA-Fe3O4 nanorods were obtained as about 29 ± 1 and 39 ± 1 nm, respectively. The hydrodynamic radius of nanorods is found as 116 nm (OA-Fe3O4) and 77 nm (Fe3O4) by DLS measurement. Cytotoxicity of Fe3O4 and OA-Fe3O4 nanorods has been investigated in the presence of human epithelial kidney (HEK) cell line 293 using MTT assay. The cell viability and proliferation studies reveal that the OA-Fe3O4 nanorods facilitate cell growth. The results of electrochemical response studies of the fabricated BSA/Ab/OA-Fe2O3/ITO immunosensor exhibits good linearity in the range of 12.5-500 ng mL-1 with low detection limit of 0.5 ng mL-1, sensitivity 0.1 ω ng-1ml-1 cm-2 and reproducibility more than 11 times. © 2015 Elsevier Ireland Ltd.
PubMed | The Interdisciplinary Center, Jawaharlal Nehru UniversityNew Delhi and National Institute of Plant Genome Research New Delhi
Type: | Journal: Frontiers in plant science | Year: 2016
Homeobox transcription factors are well known regulators of plant growth and development. In this study, we carried out functional analysis of two candidate stress-responsive HD-ZIP I class homeobox genes from rice, OsHOX22, and OsHOX24. These genes were highly up-regulated under various abiotic stress conditions at different stages of rice development, including seedling, mature and reproductive stages. The transcript levels of these genes were enhanced significantly in the presence of plant hormones, including abscisic acid (ABA), auxin, salicylic acid, and gibberellic acid. The recombinant full-length and truncated homeobox proteins were found to be localized in the nucleus. Electrophoretic mobility shift assay established the binding of these homeobox proteins with specific DNA sequences, AH1 (CAAT(A/T)ATTG) and AH2 (CAAT(C/G)ATTG). Transactivation assays in yeast revealed the transcriptional activation potential of full-length OsHOX22 and OsHOX24 proteins. Homo- and hetero-dimerization capabilities of these proteins have also been demonstrated. Further, we identified putative novel interacting proteins of OsHOX22 and OsHOX24 via yeast-two hybrid analysis. Over-expression of OsHOX24 imparted higher sensitivity to stress hormone, ABA, and abiotic stresses in the transgenic Arabidopsis plants as revealed by various physiological and phenotypic assays. Microarray analysis revealed differential expression of several stress-responsive genes in transgenic lines as compared to wild-type. Many of these genes were found to be involved in transcriptional regulation and various metabolic pathways. Altogether, our results suggest the possible role of OsHOX22/OsHOX24 homeobox proteins as negative regulators in abiotic stress responses.