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

Authors
Taeg Kyu Kwon
Department
Dept. of Immunology (면역학)
Issue Date
2001
Citation
Biochemical and Biophysical Research Communications, Vol.287(1) : 135-141, 2001
ISSN
0006-291X
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
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35175
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
Keimyung Author(s)
권택규
Full Text
https://linkinghub.elsevier.com/retrieve/pii/S0006291X01955317
File in this Item
 사서에게 요청하기
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE