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Oxidation-triggered c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways for apoptosis in human leukaemic cells stimulated by epigallocatechin-3-gallate (EGCG): a distinct pathway from those of chemically induced and receptor-mediated apoptosis.
Biochem J 2002; 368(Pt 3):705-20BJ

Abstract

We investigated intracellular signalling pathways for apoptosis induced by epigallocatechin-3-gallate (EGCG) as compared with those induced by a toxic chemical substance (etoposide, VP16) or the death receptor ligand [tumour necrosis factor (TNF)]. EGCG as well as VP16 and TNF induced activation of two apoptosis-regulating mitogen-activated protein (MAP) kinases, namely c-Jun N-terminal kinase (JNK) and p38 MAP kinase, in both human leukaemic U937 and OCI-AML1a cells. In U937 cells, the apoptosis and activation of caspases-3 and -9 induced by EGCG but not VP16 and TNF were inhibited with SB203580, a specific inhibitor of p38, while those induced by EGCG and VP16 but not TNF were inhibited with SB202190, a rather broad inhibitor of JNK and p38. In contrast, the EGCG-induced apoptosis in OCI-AML1a cells was resistant to SB203580 but not to SB202190. Unlike TNF, EGCG did not induce the activation of nuclear factor-kappaB but rather induced the primary activation of caspase-9. N -Acetyl-L-cysteine (NAC) almost completely abolished apoptosis induced by EGCG under conditions in which the apoptosis induced by VP16 or TNF was not affected. The JNK/p38 activation by EGCG was also potently inhibited by NAC, whereas those by VP16 and TNF were either not or only minimally affected by NAC. In addition, dithiothreitol also suppressed both apoptosis and JNK/p38 activation by EGCG, and EGCG-induced activation of MAP kinase kinase (MKK) 3/6, MKK4 and apoptosis-regulating kinase 1 (ASK1) was suppressed by NAC. Dominant negative ASK1, MKK6, MKK4 and JNK1 potently inhibited EGCG-induced cell death. EGCG induced an intracellular increase in reactive oxygen species and GSSG, both of which were also inhibited by NAC, and the decreased synthesis of glutathione rendered the cell susceptible to EGCG-induced apoptosis. Taken together these results strongly suggest that EGCG executed apoptotic cell death via an ASK1, MKK and JNK/p38 cascade which is triggered by NAC-sensitive intracellular oxidative events in a manner distinct from chemically induced or receptor-mediated apoptosis.

Authors+Show Affiliations

Department of Haematology, Research Institute, International Medical Centre of Japan, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12206715

Citation

Saeki, Koichi, et al. "Oxidation-triggered c-Jun N-terminal Kinase (JNK) and P38 Mitogen-activated Protein (MAP) Kinase Pathways for Apoptosis in Human Leukaemic Cells Stimulated By Epigallocatechin-3-gallate (EGCG): a Distinct Pathway From Those of Chemically Induced and Receptor-mediated Apoptosis." The Biochemical Journal, vol. 368, no. Pt 3, 2002, pp. 705-20.
Saeki K, Kobayashi N, Inazawa Y, et al. Oxidation-triggered c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways for apoptosis in human leukaemic cells stimulated by epigallocatechin-3-gallate (EGCG): a distinct pathway from those of chemically induced and receptor-mediated apoptosis. Biochem J. 2002;368(Pt 3):705-20.
Saeki, K., Kobayashi, N., Inazawa, Y., Zhang, H., Nishitoh, H., Ichijo, H., ... Yuo, A. (2002). Oxidation-triggered c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways for apoptosis in human leukaemic cells stimulated by epigallocatechin-3-gallate (EGCG): a distinct pathway from those of chemically induced and receptor-mediated apoptosis. The Biochemical Journal, 368(Pt 3), pp. 705-20.
Saeki K, et al. Oxidation-triggered c-Jun N-terminal Kinase (JNK) and P38 Mitogen-activated Protein (MAP) Kinase Pathways for Apoptosis in Human Leukaemic Cells Stimulated By Epigallocatechin-3-gallate (EGCG): a Distinct Pathway From Those of Chemically Induced and Receptor-mediated Apoptosis. Biochem J. 2002 Dec 15;368(Pt 3):705-20. PubMed PMID: 12206715.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidation-triggered c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways for apoptosis in human leukaemic cells stimulated by epigallocatechin-3-gallate (EGCG): a distinct pathway from those of chemically induced and receptor-mediated apoptosis. AU - Saeki,Koichi, AU - Kobayashi,Norihiko, AU - Inazawa,Yuko, AU - Zhang,Hong, AU - Nishitoh,Hideki, AU - Ichijo,Hidenori, AU - Saeki,Kumiko, AU - Isemura,Mamoru, AU - Yuo,Akira, PY - 2002/09/03/accepted PY - 2002/08/19/revised PY - 2002/01/15/received PY - 2002/12/6/pubmed PY - 2003/2/11/medline PY - 2002/12/6/entrez SP - 705 EP - 20 JF - The Biochemical journal JO - Biochem. J. VL - 368 IS - Pt 3 N2 - We investigated intracellular signalling pathways for apoptosis induced by epigallocatechin-3-gallate (EGCG) as compared with those induced by a toxic chemical substance (etoposide, VP16) or the death receptor ligand [tumour necrosis factor (TNF)]. EGCG as well as VP16 and TNF induced activation of two apoptosis-regulating mitogen-activated protein (MAP) kinases, namely c-Jun N-terminal kinase (JNK) and p38 MAP kinase, in both human leukaemic U937 and OCI-AML1a cells. In U937 cells, the apoptosis and activation of caspases-3 and -9 induced by EGCG but not VP16 and TNF were inhibited with SB203580, a specific inhibitor of p38, while those induced by EGCG and VP16 but not TNF were inhibited with SB202190, a rather broad inhibitor of JNK and p38. In contrast, the EGCG-induced apoptosis in OCI-AML1a cells was resistant to SB203580 but not to SB202190. Unlike TNF, EGCG did not induce the activation of nuclear factor-kappaB but rather induced the primary activation of caspase-9. N -Acetyl-L-cysteine (NAC) almost completely abolished apoptosis induced by EGCG under conditions in which the apoptosis induced by VP16 or TNF was not affected. The JNK/p38 activation by EGCG was also potently inhibited by NAC, whereas those by VP16 and TNF were either not or only minimally affected by NAC. In addition, dithiothreitol also suppressed both apoptosis and JNK/p38 activation by EGCG, and EGCG-induced activation of MAP kinase kinase (MKK) 3/6, MKK4 and apoptosis-regulating kinase 1 (ASK1) was suppressed by NAC. Dominant negative ASK1, MKK6, MKK4 and JNK1 potently inhibited EGCG-induced cell death. EGCG induced an intracellular increase in reactive oxygen species and GSSG, both of which were also inhibited by NAC, and the decreased synthesis of glutathione rendered the cell susceptible to EGCG-induced apoptosis. Taken together these results strongly suggest that EGCG executed apoptotic cell death via an ASK1, MKK and JNK/p38 cascade which is triggered by NAC-sensitive intracellular oxidative events in a manner distinct from chemically induced or receptor-mediated apoptosis. SN - 0264-6021 UR - https://www.unboundmedicine.com/medline/citation/12206715/Oxidation_triggered_c_Jun_N_terminal_kinase__JNK__and_p38_mitogen_activated_protein__MAP__kinase_pathways_for_apoptosis_in_human_leukaemic_cells_stimulated_by_epigallocatechin_3_gallate__EGCG_:_a_distinct_pathway_from_those_of_chemically_induced_and_receptor_mediated_apoptosis_ L2 - http://www.biochemj.org/cgi/pmidlookup?view=long&pmid=12206715 DB - PRIME DP - Unbound Medicine ER -