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Phorbol Myristate Acetate Inhibits Okadaic Acid-Induced Apoptosis and Downregulation of X-Linked Inhibitor of Apoptosis in U937 Cells

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Author(s)
권택규
Alternative Author(s)
Kwon, Taeg Kyu
Publication Year
2001
Abstract
Okadaic acid is a specific inhibitor of serine/threonine protein phosphatase 1 (PP-1) and 2A (PP-2A). The phosphorylation and dephosphorylation at the serine/threonine residues on proteins play important roles in regulating gene expression, cell cycle progression, and apoptosis. In this study, phosphatase inhibitor okadaic acid induces apoptosis in U937 cells via a mechanism that appears to involve caspase 3 activation, but not modulation of Bcl-2, Bax, and Bcl-XL expression levels. Treatment with 20 or 40 nM okadaic acid for 24 h produced DNA fragmentation in U937 cells. This was associated with caspase 3 activation and PLC-γ1 degradation. Okadaic acid-induced caspase 3 activation and PLC-γ1 degradation and apoptosis were dose-dependent with a maximal effect at a concentration of 40 nM. Moreover, PMA (phorbol myristate acetate), PKC (protein kinase C) activator, protected U937 cells from okadaic acid-induced apoptosis, abrogated okadaic acid-induced caspase 3 activation, and specifically inhibited downregulation of XIAP (X-linked inhibitor of apoptosis) by okadaic acid. PMA cotreated U937 cells exhibited less cytochrome c release and sustained expression levels of the IAP (inhibitor of apoptosis) proteins during okadaic acid-induced apoptosis. In addition, these findings indicate that PMA inhibits okadaic acid-induced apoptosis by a mechanism that interferes with cytochrome c release and activity of caspase 3 that is involved in the execution of apoptosis.

Keywords
apoptosis;
okadaic acid;
PMA;
caspase 3;
IAP
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Biochemical and Biophysical Research Communications, Vol.287(1) : 135-141, 2001
Type
Article
ISSN
0006-291X
DOI
10.1006/bbrc.2001.5531
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35175
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