TY - JOUR
T1 - Methylglyoxal induces apoptosis in Jurkat leukemia T cells by activating c-jun N-terminal kinase
AU - Du, Jun
AU - Suzuki, Haruhiko
AU - Nagase, Fumihiko
AU - Akhand, Anwarul A.
AU - Yokoyama, Toshihiro
AU - Miyata, Toshio
AU - Kurokawa, Kiyoshi
AU - Nakashima, Izumi
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Caspase
KW - JNK
KW - Jurkat
KW - Methylglyoxal
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U2 - 10.1002/(SICI)1097-4644(20000501)77:2<333::AID-JCB15>3.0.CO;2-Q
DO - 10.1002/(SICI)1097-4644(20000501)77:2<333::AID-JCB15>3.0.CO;2-Q
M3 - Article
C2 - 10723098
AN - SCOPUS:0034122783
VL - 77
SP - 333
EP - 344
JO - Journal of supramolecular structure and cellular biochemistry
JF - Journal of supramolecular structure and cellular biochemistry
SN - 0730-2312
IS - 2
ER -