Project description:Our main objective was to study the changes in cDNA microarray gene expression profiles of A. thaliana plants exposed to different doses of a polymetallic solution containing Pb (II), Hg (II), Cu (II), Cd (II), Co (II), Ni (II), Zn (II) and Mn (II) over 3 hours. Control plants grown in the absence of metals were also included in the experiment.
Project description:Given that transition metals are essential cofactors in central biological processes, misallocation of the wrong metal ion to a metalloprotein can have resounding and often detrimental effects on diverse aspects of cellular physiology. Therefore, in an attempt to characterize unique and shared responses to chemically similar metals we have reconstructed physiological behaviors of Halobacterium NRC-1, an archaeal halophile, in sub-lethal levels of Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II). Over 20% of all genes responded transiently within minutes of exposure to Fe(II), perhaps reflecting immediate large scale physiological adjustments to maintain homeostasis. At steady state, each transition metal induced growth arrest, attempts to minimize oxidative stress, toxic ion scavenging, increased protein turnover and DNA repair, and modulation of active ion transport. While several of these constitute generalized stress responses, up regulation of active efflux of Co(II), Ni(II), Cu(II), and Zn(II), down regulation of Mn(II) uptake and up regulation of Fe(II) chelation, confer resistance to the respective metals. We have synthesized all these discoveries into a unified systems level model to provide an integrated perspective of responses to six transition metals with emphasis on experimentally verified regulatory mechanisms. Finally, through comparisons across global transcriptional responses to different metals we provide insights into putative in vivo metal selectivity of metalloregulatory proteins and demonstrate that a systems approach can help rapidly unravel novel metabolic potential and regulatory programs of poorly studied organisms. Keywords: stress response, dose response
Project description:EDTA-Plasma from 110 hemodialysis patients participating in an NIDDK funded study were analyzed by ICP-MS for the concentration of As, Cd, Co, Cr, Cu, Mn, Mo, Ni, Pb, Sb, Se, Sn, V, and Zn. Associations were determined between trace metals and gender, race, hemodialysis status, hemoglobin at the time of draw (Hgb), total ESA dose for the month the sample was collected (EPO), and erythropoietin resistance index determined over the 6 months of treatment leading up to sample collection (ERI)
Project description:Given that transition metals are essential cofactors in central biological processes, misallocation of the wrong metal ion to a metalloprotein can have resounding and often detrimental effects on diverse aspects of cellular physiology. Therefore, in an attempt to characterize unique and shared responses to chemically similar metals we have reconstructed physiological behaviors of Halobacterium NRC-1, an archaeal halophile, in sub-lethal levels of Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II). Over 20% of all genes responded transiently within minutes of exposure to Fe(II), perhaps reflecting immediate large scale physiological adjustments to maintain homeostasis. At steady state, each transition metal induced growth arrest, attempts to minimize oxidative stress, toxic ion scavenging, increased protein turnover and DNA repair, and modulation of active ion transport. While several of these constitute generalized stress responses, up regulation of active efflux of Co(II), Ni(II), Cu(II), and Zn(II), down regulation of Mn(II) uptake and up regulation of Fe(II) chelation, confer resistance to the respective metals. We have synthesized all these discoveries into a unified systems level model to provide an integrated perspective of responses to six transition metals with emphasis on experimentally verified regulatory mechanisms. Finally, through comparisons across global transcriptional responses to different metals we provide insights into putative in vivo metal selectivity of metalloregulatory proteins and demonstrate that a systems approach can help rapidly unravel novel metabolic potential and regulatory programs of poorly studied organisms. Keywords: stress response, dose response 4 samples were analyzed. Each sample was dye-swapped (2 replicates per condition) and hybridized against a standard control.
Project description:Given that transition metals are essential cofactors in central biological processes, misallocation of the wrong metal ion to a metalloprotein can have resounding and often detrimental effects on diverse aspects of cellular physiology. Therefore, in an attempt to characterize unique and shared responses to chemically similar metals we have reconstructed physiological behaviors of Halobacterium NRC-1, an archaeal halophile, in sub-lethal levels of Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II). Over 20% of all genes responded transiently within minutes of exposure to Fe(II), perhaps reflecting immediate large scale physiological adjustments to maintain homeostasis. At steady state, each transition metal induced growth arrest, attempts to minimize oxidative stress, toxic ion scavenging, increased protein turnover and DNA repair, and modulation of active ion transport. While several of these constitute generalized stress responses, up regulation of active efflux of Co(II), Ni(II), Cu(II), and Zn(II), down regulation of Mn(II) uptake and up regulation of Fe(II) chelation, confer resistance to the respective metals. We have synthesized all these discoveries into a unified systems level model to provide an integrated perspective of responses to six transition metals with emphasis on experimentally verified regulatory mechanisms. Finally, through comparisons across global transcriptional responses to different metals we provide insights into putative in vivo metal selectivity of metalloregulatory proteins and demonstrate that a systems approach can help rapidly unravel novel metabolic potential and regulatory programs of poorly studied organisms. Keywords: stress response, dose responseH 4 samples were analyzed. Each sample was dye-swapped (2 replicates per condition) and hybridized against a standard control
Project description:Given that transition metals are essential cofactors in central biological processes, misallocation of the wrong metal ion to a metalloprotein can have resounding and often detrimental effects on diverse aspects of cellular physiology. Therefore, in an attempt to characterize unique and shared responses to chemically similar metals we have reconstructed physiological behaviors of Halobacterium NRC-1, an archaeal halophile, in sub-lethal levels of Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II). Over 20% of all genes responded transiently within minutes of exposure to Fe(II), perhaps reflecting immediate large scale physiological adjustments to maintain homeostasis. At steady state, each transition metal induced growth arrest, attempts to minimize oxidative stress, toxic ion scavenging, increased protein turnover and DNA repair, and modulation of active ion transport. While several of these constitute generalized stress responses, up regulation of active efflux of Co(II), Ni(II), Cu(II), and Zn(II), down regulation of Mn(II) uptake and up regulation of Fe(II) chelation, confer resistance to the respective metals. We have synthesized all these discoveries into a unified systems level model to provide an integrated perspective of responses to six transition metals with emphasis on experimentally verified regulatory mechanisms. Finally, through comparisons across global transcriptional responses to different metals we provide insights into putative in vivo metal selectivity of metalloregulatory proteins and demonstrate that a systems approach can help rapidly unravel novel metabolic potential and regulatory programs of poorly studied organisms. Keywords: time series
Project description:Three new complexes bearing the tridentate hydrazone-based ligand 2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)pyridine (L) were synthesized and structurally characterized. Biological tests indicate that the Zn(II) complex [ZnCl2(L)] • 0.5 H2O is of low cytotoxicity against the hepatocellular carcinoma cell line HepG2. In contrast, the Cu(II) and Mn(II) complexes [CuCl2(L)] and [MnCl2(L)(OH2)] • H2O are highly cytotoxic with EC50 values of 1.25 0.01 M and 20 1 M, respectively. A quantitative proteome analysis reveals that treatment of the cells with the Cu(II) complex leads to a significantly altered abundance of 102 apoptosis-related proteins, whereas 38 proteins were up- or down-regulated by the Mn(II) complex. A closer inspection of those proteins regulated only by the Cu(II) complex suggests that the superior cytotoxic activity of this complex is likely to be related to an initiation of caspase-independent cell death (CICD).
Project description:Given that transition metals are essential cofactors in central biological processes, misallocation of the wrong metal ion to a metalloprotein can have resounding and often detrimental effects on diverse aspects of cellular physiology. Therefore, in an attempt to characterize unique and shared responses to chemically similar metals we have reconstructed physiological behaviors of Halobacterium NRC-1, an archaeal halophile, in sub-lethal levels of Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II). Over 20% of all genes responded transiently within minutes of exposure to Fe(II), perhaps reflecting immediate large scale physiological adjustments to maintain homeostasis. At steady state, each transition metal induced growth arrest, attempts to minimize oxidative stress, toxic ion scavenging, increased protein turnover and DNA repair, and modulation of active ion transport. While several of these constitute generalized stress responses, up regulation of active efflux of Co(II), Ni(II), Cu(II), and Zn(II), down regulation of Mn(II) uptake and up regulation of Fe(II) chelation, confer resistance to the respective metals. We have synthesized all these discoveries into a unified systems level model to provide an integrated perspective of responses to six transition metals with emphasis on experimentally verified regulatory mechanisms. Finally, through comparisons across global transcriptional responses to different metals we provide insights into putative in vivo metal selectivity of metalloregulatory proteins and demonstrate that a systems approach can help rapidly unravel novel metabolic potential and regulatory programs of poorly studied organisms. Keywords: stress response, dose response, gene knockout