• Sonuç bulunamadı

Activation of c-jun NH2-terminal kinase and subsequent CPP32/Yama during topoisomerase inhibitor -lapachone-induced apoptosis through an oxidation-dependent pathway.

N/A
N/A
Info
İndir
Protected

Academic year: 2021

Share "Activation of c-jun NH2-terminal kinase and subsequent CPP32/Yama during topoisomerase inhibitor -lapachone-induced apoptosis through an oxidation-dependent pathway."

Copied!
1
0
0

Yükleniyor.... (view fulltext now)

Şimdi indir ( 1 sayfa )

Tam metin

(1)

Activation of c-jun NH2-terminal kinase and

subsequent CPP32/Yama during topoisomerase

inhibitor -lapachone-induced apoptosis through an

oxidation-dependent pathway.

沈杏娟

Shiah GS;Chuang SE;Chau YP;Shen SC and Kuo ML

Abstract

ß-Lapachone (ß-Lap) has been found to inhibit DNA topoisomerases (Topos) by a mechanism distinct from that of other commonly known Topo inhibitors. Here, we demonstrated a pronounced elevation of H2O2 and O2- in human leukemia HL-60 cells treated with ß-Lap. Treatment with other Topo poisons, such as camptothecin (CPT), VP-16, and GL331, did not have the same effect. On the other hand, antioxidant vitamin C (Vit C) treatment effectively antagonized ß-Lap-induced apoptosis. This suggested that a reactive oxygen species (ROS)-related pathway was involved in ß-Lap-induced apoptosis program. We also found that c-Jun NH2-terminal kinase (JNK) but not p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 was persistently activated in apoptosis induced by ß-Lap. Overexpression of a dominant-negative mutant

mitogen-activated protein kinase kinase kinase 1 (MEKK1-DN) or treatment with JNK-specific antisense oligonucleotide or Vit C all prevented ß-Lap-induced JNK activation and the subsequent apoptosis. Only the expression of MEKK1-DN, not Vit C treatment, blocked the JNK activity induced by CPT, VP-16, or GL331. These results confirm again that ROS acts as a mediator for JNK activation during ß-Lap-induced apoptosis. Furthermore, we found that ß-Lap can stimulate CPP32/Yama activity, which was, however, markedly inhibited by the MEKK1-DN expression or Vit C treatment. Again, CPT-induced CPP32/Yama activation can be abolished by MEKK1-DN but not by Vit C treatment. Taken together, these results indicate that ß-Lap but not other Topo inhibitors triggers apoptosis signaling, i.e., JNK and subsequent CPP32/Yama activation are mediated by the generation of ROS.

Referanslar

Şimdi indir ( PDF - 1 sayfa - 35.44 KB )

Benzer Belgeler

12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via activation of protein kinase C and JNKs in human leukemia cells

In addition, PKC inhibitor GF-109203X treatment blocks TPA- induced ERKs and JNKs protein phosphorylation, which indicates that activation of PKC locates at

12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via activation of protein kinase C and JNKs in human leukemia cells

TPA addition induces the phosphorylation of JNKs and ERKs, but not p38, protein in HL-60 cells, and incubation of HL-60 cells with JNKs inhibitor SP600125, but not ERKs inhibitor,

12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via activation of protein kinase C and JNKs in human leukemia cells

TPA addition in- duces the phosphorylation of JNKs and ERKs, but not p38, protein in HL-60 cells, and incubation of HL-60 cells with JNKs inhibitor SP600125, but not ERKs

JAVA ortamında bulanık mantık kontrol: Kamyon yükleme-boşaltma uygulaması

Simülasyonla, Mamdani ve Larsen tip bulanık içermelerin aynı nokta ve aynı açıda karşılaştırılması Şekil 4.8(a) ve 4.8(b)’de, ayrıca, bu iki bulanık

Activation of p38 mitogen-activated protein kinase in spinal microglia contributesto incision-induced mechanical allodynia

Methods: After rats received a plantar incision surgery, mechanical allodynia and thermal hyperalgesia were determined by von Frey filaments and radiant heat, respectively, and

Amyloid beta peptide increases DP5 expression via activation of neutral sphingomyelinase and JNK in oligodendrocytes.

We provide evidence that the Jun N-terminal kinase (JNK) signaling pathway mediates Aβ- and ceramide-induced apoptosis: Both Aβ and ceramide activated JNK phosphorylation,

Apoptosis signal-regulating kinase 1 mediates denbinobin-induced apoptosis in human lung adenocarcinoma cells

Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN), two antioxidants (N-acetyl-L-cysteine (NAC) and glutathione (GSH)), a c-Jun

Casein kinase II and protein kinase C modulate hepatitis delta virus RNA replication but not empty viral particle assembly

To further examine the role of phosphorylation in HDAg function, two conservative CKII recognition sites at Ser-2 and Ser-123 of both HDAgs and one potential PKC recognition site