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.
Highlights
Apoptosis or programmed cell death is a naturally occuring event found in healthy organisms (Ellis et al, 1991)
We examined the changes of phospholipase D (PLD) activity during the courses of the receptor-mediated apoptosis
Effects of tumor necrosis factor (TNF)-α and anti-Fas monoclonal antibody on PLD activity When HL-60 cells prelabeled with [3H]-palmitic acid were challenged with TNF-α for PLD activation in the presence of 1% ethanol, [3H]-PEt was produced as a result of PLDcatalyzed transphosphatidylation reaction
Summary
Apoptosis or programmed cell death is a naturally occuring event found in healthy organisms (Ellis et al, 1991). Since the polypeptide can induce divergent responses in various cell types including stimulation of proliferation, differentiation and death, it may activate multiple signaling pathways in different cell types (Wright et al, 1992). The activation of Fas/Apo recep-tor can elicit apoptosis in mouse thymus (Watanabe-Fukanaga et al, 1992) and these TNF homologous receptors have been thought to transmit a common signal leading to apoptosis. There are several lines of evidence suggesting that the apoptotic process involves signal transduction mechanism found in embryonic development and cell proliferation (Dowd et al, 1992; Song et al, 1992). A question has arisen whether PLD might be involved in TNF receptor- and Fas-mediated apoptosis, a yet another important biological phenomenon in eukaryotic cells. We examined the changes of PLD activity during the courses of the receptor-mediated apoptosis
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