Participation of various kinases in staurosporine-induced apoptosis of RAW 264.7 cells

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‐G1 cel...

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Bibliographic Details
Published in:	Journal of pharmacy and pharmacology Vol. 54; no. 11; pp. 1535 - 1544
Main Authors:	Yamaki, Kouya, Hong, JangJa, Hiraizumi, Kenji, Ahn, Jong Woon, Zee, OkPyo, Ohuchi, Kazuo
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-11-2002 Pharmaceutical Press
Subjects:	Ageing, cell death Animals Apoptosis Biological and medical sciences Caspases - metabolism Cell Line Cell physiology Chromones - pharmacology DNA Fragmentation - drug effects Enzyme Activation - drug effects Enzyme Inhibitors - pharmacology Flavonoids - pharmacology Fundamental and applied biological sciences. Psychology General and cellular metabolism. Vitamins Isoquinolines - pharmacology Macrophages - cytology Macrophages - drug effects Macrophages - enzymology Medical sciences Mice Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinases - metabolism Molecular and cellular biology Morpholines - pharmacology p38 Mitogen-Activated Protein Kinases Pharmacology. Drug treatments Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphorylation Protein Kinase C - antagonists & inhibitors Staurosporine - pharmacology Sulfonamides Phosphorylation Protein kinase C Enzyme Transferases Rodentia Caspase Enzyme inhibitor Mitogen-activated protein kinase Activation In vitro Peptidases Vertebrata Mammalia Mouse Cell death Animal Established cell line Hydrolases Mechanism of action Apoptosis Macrophage
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Summary:	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‐G1 cells revealed that the DNA fragmentation occurred in a time‐ and concentration‐dependent manner at 0.021–2.1 μm 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 (P13K) 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 P13K via the caspase cascade, and negatively regulated by PKA without regulation of caspase activation.
Bibliography:	ark:/67375/WNG-JCSC13BR-9 istex:89DC91E7049B39C65171019C559B66DA7BA5B714 ArticleID:JPHP2223 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3573 2042-7158
DOI:	10.1211/002235702144