Changes of phospholipase D activity in TNF-alpha and anti-Fas/Apo1 monoclonal antibody induced apoptosis in HL-60 and A20 cells.
- Author:
Jin Ho KANG
1
;
In Cheol SHIN
;
Joong Soo HAN
Author Information
1. Department of Biochemistry, College of Medicine, Hanyang University, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
anti-Fas monoclonal antibody;
phospholipase D;
protein kinase C;
tumor necrosis factor-alpha
- MeSH:
Animal;
Antibodies, Monoclonal/pharmacology;
Antigens, CD95/metabolism*;
Antigens, CD95/immunology;
Apoptosis*;
DNA Fragmentation;
Dose-Response Relationship, Drug;
Enzyme Activation;
HL-60 Cells;
Human;
Leukemia, Promyelocytic, Acute;
Lymphoma, B-Cell;
Mice;
Naphthalenes/pharmacology;
Phospholipase D/metabolism*;
Protein Kinase C/antagonists & inhibitors;
Receptors, Tumor Necrosis Factor/metabolism*;
Signal Transduction;
Tumor Necrosis Factor/pharmacology*
- From:Experimental & Molecular Medicine
1998;30(1):21-27
- CountryRepublic of Korea
- Language:English
-
Abstract:
The changes of phospholipase D (PLD) activity were investigated during the courses of apoptotic process induced by tumor necrosis factor (TNF)-alpha or anti-Fas/Apo1 antibody in human premyelocyte HL-60 and murine B cell lymphoma A20 cells. The treatment of recombinant TNF-alpha to HL-60 cells resulted in the increased PLD activity as determined by the phosphatidylethanol formation in the presence of 1% ethanol. The enhancement of PLD activity was also observed in the anti-Fas/Apo1 monoclonal antibody-treated A20 cells. However, the activity of PLD was maximized when HL-60 and A20 cells were treated with either TNF-alpha or anti-Fas/Apo1 monoclonal antibody for 6 h. Both TNF-alpha and anti-Fas/Apo1 monoclonal antibody increased PLD activity in a dose-dependent manner up to 200 U/ml and 200 ng/ml, respectively. When the intracellular activity of protein kinase C (PKC) was interrupted by treatment of calphostin-C, both the PLD activation and the apoptosis induced by TNF-alpha and anti-Fas/Apo1 monoclonal antibody appeared to be inhibited. Since PKC is reported to activate PLD, the results indicate that the intracellular signaling cascade via PLD may play a role in the induction of apoptosis induced by TNF-alpha and anti-Fas/Apo1 monoclonal antibody.