Lead exposure and heat shock inhibit cell proliferation in human HeLa and K562 cells by inducing expression and activity of the heme-regulated eIF-2alpha kinase. 2002

Angshuman Sarkar, and Samit Chattopadhyay, and Ruchika Kaul, and Jayanta K Pal
Department of Biotechnology, Cell and Molecular Biology Research Laboratory, University of Pune, Pune-411 007, India.

We have used human cell lines, namely, K562 and HeLa cells as model systems in understanding the mechanism of lead toxicity and heat shock, that may be mediated by the heme-regulated eIF-2alpha kinase which is also called the heme-regulated inhibitor (HRI). RT-PCR analysis using HRI-specific primers indicated a two- to three-fold increase in HRI expression in K562 and HeLa cells exposed to lead acetate and heat shock, respectively. Further, in vitro eIF-2alpha kinase assay indicated a two- to three-fold increase in HRI kinase activity during lead toxicity in K562 cells. This increase in HRI expression and its activity was accompanied by a significant decrease in cell proliferation and cell viability. This is therefore, the first report indicating that both heavy metal exposure and heat shock cause inhibition of protein synthesis not by activation of HRI alone but by its over-expression as well as activation. Our data indicate further that lead-induced inhibition of cell proliferation may be caused due to inhibition of protein synthesis resulted due to induced expression and activity of HRI.

UI MeSH Term Description Entries
D007854 Lead A soft, grayish metal with poisonous salts; atomic number 82, atomic weight 207.2, symbol Pb.
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006358 Hot Temperature Presence of warmth or heat or a temperature notably higher than an accustomed norm. Heat,Hot Temperatures,Temperature, Hot,Temperatures, Hot
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000222 Adaptation, Physiological The non-genetic biological changes of an organism in response to challenges in its ENVIRONMENT. Adaptation, Physiologic,Adaptations, Physiologic,Adaptations, Physiological,Adaptive Plasticity,Phenotypic Plasticity,Physiological Adaptation,Physiologic Adaptation,Physiologic Adaptations,Physiological Adaptations,Plasticity, Adaptive,Plasticity, Phenotypic
D015971 Gene Expression Regulation, Enzymologic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis. Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic
D018869 Heat-Shock Response A sequence of responses that occur when an organism is exposed to excessive heat. In humans, an increase in skin temperature triggers muscle relaxation, sweating, and vasodilation. Heat-Shock Reaction,Heat Shock,Heat Shock Stress,Heat Stress,Heat-Stress Reaction,Heat-Stress Response,Heat Shock Reaction,Heat Shock Response,Heat Shock Stresses,Heat Shocks,Heat Stress Reaction,Heat Stress Response,Heat Stresses,Heat-Shock Reactions,Heat-Shock Responses,Heat-Stress Reactions,Heat-Stress Responses,Shock, Heat,Stress, Heat,Stress, Heat Shock
D019892 eIF-2 Kinase A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis. Protein Kinase PKR,Protein Kinase, RNA Activated,RNA-Dependent Protein Kinase,p68 Kinase,DAI Protein Kinase,DSRNA-Dep Protein Kinase,Double Stranded RNA-Dependent Kinase (dsl),Double Stranded RNA-Dependent eIF-2 alpha Protein Kinase,Eukaryotic Initiation Factor 2alpha Kinase,Heme Controlled Repressor,Heme-Controlled Inhibitor,Heme-Controlled Translational Repressor,Heme-Regulated eIF-2alpha Kinase,Hemin Controlled Repressor,Hemin-Controlled Translational Repressor,P68 Protein Kinase,Self-Phosphorylating Protein Kinase,TIK Kinase,dsRNA-Activated Inhibitor,eIF-2alpha Kinase,eRF, eIF-2 Recycling Factor,p65 Kinase,Controlled Repressor, Heme,Controlled Repressor, Hemin,DSRNA Dep Protein Kinase,Double Stranded RNA Dependent eIF 2 alpha Protein Kinase,Heme Controlled Inhibitor,Heme Controlled Translational Repressor,Heme Regulated eIF 2alpha Kinase,Hemin Controlled Translational Repressor,Inhibitor, Heme-Controlled,Inhibitor, dsRNA-Activated,Kinase PKR, Protein,Kinase, DAI Protein,Kinase, DSRNA-Dep Protein,Kinase, Heme-Regulated eIF-2alpha,Kinase, P68 Protein,Kinase, RNA-Dependent Protein,Kinase, Self-Phosphorylating Protein,Kinase, TIK,Kinase, eIF-2,Kinase, eIF-2alpha,Kinase, p65,Kinase, p68,PKR, Protein Kinase,Protein Kinase, DAI,Protein Kinase, DSRNA-Dep,Protein Kinase, P68,Protein Kinase, RNA-Dependent,Protein Kinase, Self-Phosphorylating,RNA Dependent Protein Kinase,Repressor, Heme Controlled,Repressor, Heme-Controlled Translational,Repressor, Hemin Controlled,Repressor, Hemin-Controlled Translational,Self Phosphorylating Protein Kinase,Translational Repressor, Heme-Controlled,Translational Repressor, Hemin-Controlled,dsRNA Activated Inhibitor,eIF 2 Kinase,eIF 2alpha Kinase,eIF-2alpha Kinase, Heme-Regulated,eRF, eIF 2 Recycling Factor

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