RRC ID 41754
Author Yamaki K, Hong J, Hiraizumi K, Ahn JW, Zee O, Ohuchi K.
Title Participation of various kinases in staurosporine induced apoptosis of RAW 264.7 cells.
Journal J Pharm Pharmacol
Abstract Staurosporine induced apoptosis of RAW 264.7 cells, a mouse macrophage-like cell line, as determined by DNA fragmentation, the increase of annexin V-stained cells, and the cleavage of poly(ADP-ribose)polymerase (PARP), a substrate of caspase. Analysis of the increase in the percentage of sub-G(1) cells revealed that the DNA fragmentation occurred in a time- and concentration-dependent manner at 0.021-2.1 microM of staurosporine. Staurosporine induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) but suppressed spontaneous phosphorylation of p44/42 MAPK. The p38 MAPK inhibitor SB203580, the MAPK/extracellular signal-regulated kinase kinase inhibitor PD98059 and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 potentiated the staurosporine-induced PARP cleavage and DNA fragmentation. The protein kinase A (PKA) inhibitor H-89 potentiated the staurosporine-induced DNA fragmentation without potentiating the PARP cleavage. In contrast, the protein kinase C (PKC) inhibitor Ro-31-8425 suppressed the PARP cleavage and DNA fragmentation. These findings suggested that staurosporine induces apoptosis via the caspase cascade in RAW 264.7 cells. The staurosporine-induced apoptosis is positively regulated by PKC, negatively regulated by p38 MAPK, p44/42 MAPK and PI3K via the caspase cascade, and negatively regulated by PKA without regulation of caspase activation.
Volume 54(11)
Pages 1535-44
Published 2002-11-1
DOI 10.1211/002235702144
PMID 12495557
MeSH Animals Apoptosis* Caspases / metabolism Cell Line Chromones / pharmacology DNA Fragmentation / drug effects Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology* Flavonoids / pharmacology Isoquinolines / pharmacology Macrophages / cytology Macrophages / drug effects Macrophages / enzymology Mice Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinases / metabolism Morpholines / pharmacology Phosphoinositide-3 Kinase Inhibitors Phosphorylation Protein Kinase C / antagonists & inhibitors Staurosporine / pharmacology* Sulfonamides* p38 Mitogen-Activated Protein Kinases
IF 2.39
Times Cited 22
Human and Animal Cells