Document Detail

Mechanism underlying cytotoxicity of thialysine, lysine analog, toward human acute leukemia Jurkat T cells.
MedLine Citation:
PMID:  14637187     Owner:  NLM     Status:  MEDLINE    
We first report the mechanism for the inhibitory effect of the lysine analog, thialysine on human acute leukemia Jurkat T cells. When Jurkat T cells were treated with thialysine (0.32-2.5 mM), apoptotic cell death along with several biochemical events such as mitochondrial cytochrome c release, caspase-9 activation, caspase-3 activation, degradation of poly (ADP-ribose) polymerase, and DNA fragmentation was induced in a dose- and time-dependent manner. However, these thialysine-induced apoptotic events were significantly abrogated by an ectopic expression of Bcl-xL, which is known to block mitochondrial cytochrome c release. Decylubiquinone, a mitochondrial permeability transition pore inhibitor, also suppressed thialysine-induced apoptotic events. Comparison of the thialysine-induced alterations in the cell cycle distribution between Jurkat T cells transfected with Bcl-xL gene (J/Bcl-xL) and Jurkat T cells transfected with vector (J/Neo) revealed that the apoptotic cells were mainly derived from the cells accumulated in S and G2/M phases following thialysine treatment. The interruption of cell cycle progression in the presence of thialysine was accompanied by a significant decline in the protein level of cdk4, cdk6, cdc2, cyclin A, cyclin B1, and cyclin E. These results demonstrate that the cytotoxic activity of thialysine toward Jurkat T cells is attributable to not only apoptotic cell death mediated by a mitochondria-dependent death signaling pathway, but also interruption of cell cycle progression by a massive down-regulation in the level of cdks and cyclins.
Do Youn Jun; Seok Woo Rue; Kyu Hyun Han; Dennis Taub; Young Sup Lee; Young Seuk Bae; Young Ho Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  66     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-11-25     Completed Date:  2004-01-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2291-300     Citation Subset:  IM    
Laboratory of Immunobiology, Department of Microbiology, College of Natural Sciences, Kyungpook National University, 702-701 Taegu, South Korea.
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MeSH Terms
Caspases / metabolism
Cell Cycle / drug effects*
Cell Survival / drug effects
Cysteine / analogs & derivatives*,  pharmacology*
Cytochromes c / metabolism
Enzyme Activation / drug effects
Jurkat Cells
Lysine / chemistry*
Mitochondria / drug effects,  enzymology
Protein Synthesis Inhibitors / pharmacology*
Proto-Oncogene Proteins c-bcl-2 / pharmacology
Tumor Cells, Cultured
bcl-X Protein
Reg. No./Substance:
0/BCL2L1 protein, human; 0/Protein Synthesis Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-X Protein; 2936-69-8/S-2-aminoethyl cysteine; 52-90-4/Cysteine; 56-87-1/Lysine; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases

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