title: Cellular toxicity of cadmium ions and their detoxification by heavy metal-specific plant peptides, phytochelatins, expressed in Mammalian cells.
abstract: The apoptotic cell death of Jurkat cells due to Cd(2+) toxicity was studied by fluorescence microscopic observation and DNA fragmentation assaying. It was suggested that the apoptotic response to Cd(2+) was less clear than that to a typical apoptosis inducer, ultraviolet light (254 nm). Examination of MAP kinase phosphorylation (p38, JNKs, and c-Jun) due to Cd(2+) toxicity indicated that the phosphorylation was very slowly activated (4 h after stimulation), while UV light could activate the phosphorylation immediately. Therefore, it was suggested that Cd(2+) may not be a typical apoptosis inducer. Antioxidants [glutathione (GSH) and N-acetylcysteine (NAC)] could detoxify Cd(2+), indicating that the toxicity is a kind of oxidative stress. The detoxification effect of antioxidants showed cooperation with Bcl-2, suggesting that Cd(2+)-treatment causes diversified toxic signals including oxidative stress. On the addition of a plant-specific peptide, phytochelatin [PC(7), (gammaGlu-Cys)(7)-Gly], to the medium, the detoxification of Cd(2+) and cooperation with Bcl-2 were more intense than in the cases of GSH and NAC. Using an appropriate vector, a PC synthase gene was transferred from Arabidopsis thaliana to the Jurkat cell. The transfectant exhibited resistance to Cd(2+) and production of plant-specific PC (PC(2-6)).
authors.affiliation: School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Tatsunokuchi, Ishikawa 923-1292, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takagi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Satofuka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Amano
authors.forename: Haruo
authors.initials: H
authors.lastname: Mizuno
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Eguchi
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hirata
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Kiichi
authors.initials: K
authors.lastname: Fukui
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Imanaka
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D019881:Aminoacyltransferases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002104:Cadmium / Q000633:toxicity*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002614:Chelating Agents / Q000378:metabolism / Q000494:pharmacology*; D017931:DNA Primers / Q000737:chemistry; D004351:Drug Resistance; D016166:Free Radical Scavengers / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells / Q000187:drug effects*; D048670:MAP Kinase Kinase 4; D008667:Metalloproteins / Q000378:metabolism / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress; D054811:Phytochelatins; D010944:Plants / Q000737:chemistry; D010957:Plasmids; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D002614:Chelating Agents; D017931:DNA Primers; D016166:Free Radical Scavengers; D008667:Metalloproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D002104:Cadmium; D054811:Phytochelatins; D019881:Aminoacyltransferases; C093784:glutathione gamma-glutamylcysteinyltransferase; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D005978:Glutathione; D000111:Acetylcysteine