Influence of cadmium on murine thymocytes: potentiation of apoptosis and oxidative stress.

2.50
Hdl Handle:
http://hdl.handle.net/10146/64814
Title:
Influence of cadmium on murine thymocytes: potentiation of apoptosis and oxidative stress.
Authors:
Pathak, Neelima; Khandelwal, Shashi
Abstract:
Cadmium (Cd) is a well-known environmental carcinogen and a potent immunotoxicant. It induces thymocyte apoptosis in vitro. However, the mode of action is unclear. In this study, we examined the effect of Cd (10, 25 and 50microM) on mitochondrial membrane potential and caspase-3 as well as oxidative stress markers in murine thymocytes. The cadmium induced apoptosis occurred in a concentration and time dependent manner. The early markers of apoptosis-loss in mitochondrial membrane potential and caspase-3 activation were evident as early as 1.5h by 50microM Cd. Enhanced reactive oxygen species (ROS) generation and glutathione (GSH) depletion were observed at 60min, prior to the lowering of mitochondrial membrane potential. The Cd induced DNA damage as depicted by internucleosomal fragmentation on agarose and histone associated mono- and oligonucleosomes detection by ELISA, corrobated with the apoptotic DNA (sub-G(1) population) and total apoptotic cells by Annexin V binding assay. The number of cells in sub-G(1) population increased to 66% at 50microM Cd concentration and the distribution of early and late apoptotic cells was 47% and 15%, respectively. Addition of N-acetylcysteine and pyrrolidine dithiocarbamate (thiol antioxidants) to the Cd treated cells, lowered the sub-G(1) population, inhibited the ROS generation and raised the GSH levels. Buthionine sulfoximine (GSH depletor) on the other hand, enhanced both the ROS production and the sub-G(1) fraction. These results clearly demonstrate the apoptogenic potential of Cd in murine thymocytes, following mitochondrial membrane depolarization, caspase activation and ROS and GSH acting as critical mediators.
Citation:
Toxicol. Lett. 2006, 165 (2):121-132
Journal:
Toxicology letters
Issue Date:
20-Aug-2006
URI:
http://hdl.handle.net/10146/64814
DOI:
10.1016/j.toxlet.2006.02.004
PubMed ID:
16563667
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCR-4JDN6CS-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=9df9189faef3fd039d0315f89cf20125
Type:
Article
Language:
en
Description:
KEYWORDS CLASSIFICATION: Animals;Antimetabolites;Apoptosis;Buthionine Sulfoximine;Cadmium;Carcinogens;Carcinogens,Environmental;Caspase 3;Caspases;Cells,Cultured;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;drug effects;DNA Damage;Dose-Response Relationship,Drug;Glutathione;India;metabolism;Male;Membrane Potentials;Mice;Mice,Inbred BALB C;Mitochondria;Oxidative Stress;pathology;pharmacology;physiology;Reactive Oxygen Species;Research;toxicity;Thymus Gland;Toxicology;humans.
ISSN:
0378-4274
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorPathak, Neelima-
dc.contributor.authorKhandelwal, Shashi-
dc.date.accessioned2009-04-14T07:34:36Z-
dc.date.available2009-04-14T07:34:36Z-
dc.date.issued2006-08-20-
dc.identifier.citationToxicol. Lett. 2006, 165 (2):121-132en
dc.identifier.issn0378-4274-
dc.identifier.pmid16563667-
dc.identifier.doi10.1016/j.toxlet.2006.02.004-
dc.identifier.urihttp://hdl.handle.net/10146/64814-
dc.descriptionKEYWORDS CLASSIFICATION: Animals;Antimetabolites;Apoptosis;Buthionine Sulfoximine;Cadmium;Carcinogens;Carcinogens,Environmental;Caspase 3;Caspases;Cells,Cultured;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;drug effects;DNA Damage;Dose-Response Relationship,Drug;Glutathione;India;metabolism;Male;Membrane Potentials;Mice;Mice,Inbred BALB C;Mitochondria;Oxidative Stress;pathology;pharmacology;physiology;Reactive Oxygen Species;Research;toxicity;Thymus Gland;Toxicology;humans.en
dc.description.abstractCadmium (Cd) is a well-known environmental carcinogen and a potent immunotoxicant. It induces thymocyte apoptosis in vitro. However, the mode of action is unclear. In this study, we examined the effect of Cd (10, 25 and 50microM) on mitochondrial membrane potential and caspase-3 as well as oxidative stress markers in murine thymocytes. The cadmium induced apoptosis occurred in a concentration and time dependent manner. The early markers of apoptosis-loss in mitochondrial membrane potential and caspase-3 activation were evident as early as 1.5h by 50microM Cd. Enhanced reactive oxygen species (ROS) generation and glutathione (GSH) depletion were observed at 60min, prior to the lowering of mitochondrial membrane potential. The Cd induced DNA damage as depicted by internucleosomal fragmentation on agarose and histone associated mono- and oligonucleosomes detection by ELISA, corrobated with the apoptotic DNA (sub-G(1) population) and total apoptotic cells by Annexin V binding assay. The number of cells in sub-G(1) population increased to 66% at 50microM Cd concentration and the distribution of early and late apoptotic cells was 47% and 15%, respectively. Addition of N-acetylcysteine and pyrrolidine dithiocarbamate (thiol antioxidants) to the Cd treated cells, lowered the sub-G(1) population, inhibited the ROS generation and raised the GSH levels. Buthionine sulfoximine (GSH depletor) on the other hand, enhanced both the ROS production and the sub-G(1) fraction. These results clearly demonstrate the apoptogenic potential of Cd in murine thymocytes, following mitochondrial membrane depolarization, caspase activation and ROS and GSH acting as critical mediators.en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCR-4JDN6CS-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=9df9189faef3fd039d0315f89cf20125en
dc.subjectCadmiumen
dc.subjectMurine thymocytesen
dc.subjectApoptosisen
dc.subjectOxidative stressen
dc.subjectCaspase-3en
dc.subject.meshAnimals-
dc.subject.meshAntimetabolites-
dc.subject.meshApoptosis-
dc.subject.meshButhionine Sulfoximine-
dc.subject.meshCadmium-
dc.subject.meshCarcinogens, Environmental-
dc.subject.meshCaspase 3-
dc.subject.meshCaspases-
dc.subject.meshCells, Cultured-
dc.subject.meshDNA Damage-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshGlutathione-
dc.subject.meshMale-
dc.subject.meshMembrane Potentials-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshMitochondria-
dc.subject.meshOxidative Stress-
dc.subject.meshReactive Oxygen Species-
dc.subject.meshThymus Gland-
dc.titleInfluence of cadmium on murine thymocytes: potentiation of apoptosis and oxidative stress.en
dc.typeArticleen
dc.identifier.journalToxicology lettersen
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