Document Detail


Methylglyoxal induces apoptosis in Jurkat leukemia T cells by activating c-Jun N-terminal kinase.
MedLine Citation:
PMID:  10723098     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Methylglyoxal (MG) is a physiological metabolite, but it is known to be toxic, inducing stress in cells and causing apoptosis. This study examines molecular mechanisms in the MG-induced signal transduction leading to apoptosis, focusing particularly on the role of JNK activation. We first confirmed that MG caused apoptosis in Jurkat cells and that it was cell type dependent because it failed to induce apoptosis in MOLT-4, HeLa, or COS-7 cells. A caspase inhibitor, Z-DEVD-fmk, completely blocked MG-induced poly(ADP-ribose)polymerase (PARP) cleavage and apoptosis, showing the critical role of caspase activation. Inhibition of JNK activity by a JNK inhibitor, curcumin, remarkably reduced MG-induced caspase-3 activation, PARP cleavage, and apoptosis. Stable expression of the dominant negative mutant of JNK also protected cells against apoptosis notably, although not completely. Correspondingly, loss of the mitochondrial membrane potential induced by MG was decreased by the dominant negative JNK. These results confirmed a crucial role of JNK working upstream of caspases, as well as an involvement of JNK in affecting the mitochondrial membrane potential.
Authors:
J Du; H Suzuki; F Nagase; A A Akhand; T Yokoyama; T Miyata; K Kurokawa; I Nakashima
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  77     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-05-31     Completed Date:  2000-05-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  333-44     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Wiley-Liss, Inc.
Affiliation:
Department of Immunology, Nagoya University School of Medicine, Aichi 466-8550, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
COS Cells
Caspase 3
Caspases / antagonists & inhibitors
Cell Line
Cysteine Proteinase Inhibitors / pharmacology
Enzyme Activation / drug effects
Hela Cells
Humans
Intracellular Membranes / drug effects,  metabolism
JNK Mitogen-Activated Protein Kinases
Jurkat Cells
Membrane Potentials / drug effects
Mitochondria / drug effects,  metabolism
Mitogen-Activated Protein Kinases / genetics,  metabolism*
Mutation
Oligopeptides / pharmacology
Poly(ADP-ribose) Polymerases / metabolism
Pyruvaldehyde / toxicity*
Transfection
Chemical
Reg. No./Substance:
0/Cysteine Proteinase Inhibitors; 0/Oligopeptides; 0/benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; 78-98-8/Pyruvaldehyde; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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