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Relationship between arachidonate--phospholipid remodeling and apoptosis
M E Surette1, J D Winkler, A N Fonteh
1Section on Pulmonary and Critical Care Medicine, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27157-1054, USA.
Biochemistry
|July 16, 1996
Summary
Inhibiting CoA-independent transacylase (CoA-IT) blocks arachidonate remodeling in HL-60 cells, causing apoptosis. This phospholipid remodeling disruption triggers programmed cell death, impacting cell proliferation.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- CoA-independent transacylase (CoA-IT) plays a role in remodeling polyunsaturated fatty acids in mammalian cell phospholipids.
- Previous studies indicated that CoA-IT inhibitors induce apoptosis in HL-60 cells.
Purpose of the Study:
- To elucidate the mechanism by which CoA-IT inhibitors induce apoptosis in HL-60 cells.
- To investigate the role of arachidonate-phospholipid remodeling in CoA-IT inhibitor-induced apoptosis.
Main Methods:
- HL-60 cells were treated with CoA-IT inhibitors.
- Gas chromatography-mass spectrometry (GC-MS) was used to analyze fatty acid distribution in phospholipids.
- Transmission electron microscopy and flow cytometry assessed apoptosis markers and DNA fragmentation.
Main Results:
- CoA-IT inhibitors blocked arachidonate remodeling from choline to ethanolamine phospholipids.
- A significant redistribution of arachidonate occurred, increasing in phosphatidylcholine and decreasing in phosphatidylethanolamine.
- This redistribution was specific to arachidonate and did not affect linoleic acid or total phospholipid classes.
- Apoptosis was confirmed by characteristic cellular changes and DNA fragmentation.
Conclusions:
- Blocking arachidonate-phospholipid remodeling by inhibiting CoA-IT induces apoptosis in HL-60 cells.
- The redistribution of arachidonate in membrane phospholipids is correlated with apoptosis.
- These phospholipid alterations may signal and control cellular proliferation capacity.