共 32 条
Stress induces mitochondria-mediated apoptosis independent of SAPK/JNK activation in embryonic stem cells
被引:23
作者:

Nishitai, G
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Shimizu, N
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Negishi, T
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Kishimoto, H
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Nakagawa, K
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Kitagawa, D
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Watanabe, T
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Momose, H
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Ohata, S
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Tanemura, S
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h-index: 0
机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Asaka, S
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h-index: 0
机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Kubota, J
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Saito, R
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Yoshida, H
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Mak, TW
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Wada, T
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机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Penninger, JM
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h-index: 0
机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Azuma, N
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h-index: 0
机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Nishina, H
论文数: 0 引用数: 0
h-index: 0
机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan

Katada, T
论文数: 0 引用数: 0
h-index: 0
机构: Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan
机构:
[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Bunkyo Ku, Tokyo 1130033, Japan
[2] Saga Med Sch, Dept Biomol Sci, Saga 8498501, Japan
[3] Univ Turin, Univ Hlth Network, Dept Med Biophys, Toronto, ON M5G 2C1, Canada
[4] Univ Turin, Univ Hlth Network, Dept Immunol, Toronto, ON M5G 2C1, Canada
[5] Natl Ctr Child Hlth & Dev, Dept Ophthalmol, Setagaya Ku, Tokyo 1578535, Japan
关键词:
D O I:
10.1074/jbc.M310335200
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
SAPK/JNK, which belongs to the family of mitogen-activated protein kinase ( MAPK), is activated by many types of cellular stresses or extracellular signals and is involved in embryonic development, immune responses, and cell survival or apoptosis. However, the physiological roles of SAPK/JNK in the signaling of stress-induced apoptosis are still controversial. To evaluate the precise function, SAPK/JNK-inactivated mouse embryonic stem (ES) cells were generated by disrupting genes of the MAPK activators, SEK1 and MKK7. Although SAPK/JNK activation by various stresses was completely abolished in sek1(-/-) mkk7(-/-) ES cells, apoptotic responses including DNA fragmentation and caspase 3 activation still occurred normally, which displays a sharp contrast to apaf1(-/-) ES cells exhibiting profound defects in the mitochondria-dependent apoptosis. These normal apoptotic responses without SAPK/JNK activation were also observed in fibroblasts derived from sek1(-/-) mkk7(-/-) ES cells. Instead, interleukin-1beta (IL-1beta)- induced IL-6 gene expression was greatly suppressed in sek1(-/-) mkk7(-/-) fibroblasts. These results clearly show that SAPK/JNK activation is responsible for the inflammatory cytokine-induced gene expression but not essentially required for the mitochondria-dependent apoptosis at least in ES or fibroblast-like cells, which are prototypes of all cell lineages.
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页码:1621 / 1626
页数:6
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