RRC ID 1599
Author Nishitai G, Shimizu N, Negishi T, Kishimoto H, Nakagawa K, Kitagawa D, Watanabe T, Momose H, Ohata S, Tanemura S, Asaka S, Kubota J, Saito R, Yoshida H, Mak TW, Wada T, Penninger JM, Azuma N, Nishina H, Katada T.
Title Stress induces mitochondria-mediated apoptosis independent of SAPK/JNK activation in embryonic stem cells.
Journal J Biol Chem
Abstract 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-1 beta (IL-1 beta)-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.
Volume 279(3)
Pages 1621-6
Published 2004-1-16
DOI 10.1074/jbc.M310335200
PII S0021-9258(20)68716-6
PMID 14585831
MeSH Animals Apoptosis* Cells, Cultured Embryo, Mammalian / cytology Enzyme Activation Hot Temperature Interleukin-1 / pharmacology Interleukin-6 / genetics MAP Kinase Kinase 7 Mice Mitochondria / physiology* Mitogen-Activated Protein Kinase Kinases / physiology Mitogen-Activated Protein Kinases / physiology Stem Cells / cytology Stem Cells / enzymology p38 Mitogen-Activated Protein Kinases
IF 4.238
Times Cited 22
DNA material AxCANCre (RDB01748)