|
KMID : 0613820030130010118
|
|
Journal of Life Science
2003 Volume.13 No. 1 p.118 ~ p.127
|
|
|
Ectopic expression of Bcl-2 or Bcl-xL suppresses p-fluorophenylalanine-induced apoptosis through blocking mitochondria-dependent caspase cascade in human Jurkat T cells
|
|
Han Kyu-Hyun
Oh Hyun-Ji
Jun Do-Youn
Kim Young-Ho
|
|
|
Abstract
|
|
|
|
ρ-Fluorophenylalanine (FPA), a phenylalanine analog, is able to induce apoptotic cell death of human acute leukemia Jurkat T cells. To better understand the mechanism by which FPA induces apoptotic cell death, the effect of ectopic expression of antiapoptotic proteins, Bcl-2 and Bcl-xL, on FPA-induced apoptosis was investigated by employing Jurkat T cells transfected with Bcl-2 gene (JT/Bcl-2) or Bcl-xL gene (J/Bcl-xL) and Jurkat T cells transfected with vector (JT/Neo or J/Neo). When Jurkat T cells, JT/Neo or J/Neo, were exposed to FPA at concentrations ranging from 0.63 to 5.0 mM, the cell viability determined by MTT assay declined in a dose-dependent manner. In addition, apoptotic DNA fragmentation along with several apoptotic events such as caspase-8 activation, Bid cleavage, mitochondrial cytochrome c release, caspase-9 activation, caspase-3 activation, and degradation of PARP was induced. However, the FPA-induced cytotoxic effect, activation of caspase-8, and cleavage of Bid were significantly abrogated by ectopic expression of Bcl-2 or Bcl-xL. At the same time, there was marked reduction in the level of cytochrome c release from mitochondria, caspase-9 activation, caspase-3 activation, and degradation of PARP. These results indicate that caspase-8 activation, Bid cleavage, and mitochondrial cytochrome c release with subsequent activation of the caspase cascade are negatively regulated by Bcl-2 or Bcl-xL, and are thus required for FPA-induced apoptosis in Jurkat T cells.
|
|
|
KEYWORD
|
|
|
ρ-fluorophenylalanine, apoptosis, cytochrome c-dependent caspase cascade, Bcl-2, Bcl-xL
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|