of Work: We have used Syrian hamster embryo cells (SHE) to study the modulation of cell growth and apoptosis by lipid metabolites. EGF- dependent mitogenesis was inhibited by lipoxygenase inhibitors but not attenuated by PGHS inhibitors. EGF did not stimulate prostaglandin formation but did stimulate the metabolism of linoleic acid to 13(S)- HODE. The formation of 13-HODE is regulated by the tyrosine kinase activity of the EGF receptor but the mechanism is poorly understood. The linoleic acid metabolite potentiated EGF-dependent mitogenesis in the supB+ SHE cells but this response was lost on progression to the supB-. Structure-activity investigations revealed that 13(S)-HpODE was the most effective lipid compound in stimulating EGF-regulated DNA synthesis in SHE cells. This suggested a specific site for 13(S)-HpODE effects. Since the formation of 13(S)-HODE up-regulates EGF-dependent cell growth, we prepared stable transfectants of supB+ cells that over-express 15- lipoxygenase. This increased expression of 15-lipoxygenase and the formation of 13(S)-HpODE increases the rate of cell growth 4 fold. These findings provide additional evidence for lipid metabolites as regulators of cell proliferation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES050149-03
Application #
6162255
Study Section
Special Emphasis Panel (LMC)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code