POLYUNSATURATED FATTY ACIDS AND CELL FUNCTION

  • Knapp, Howard (PI)
  • Chappell, David (PI)
  • Weintraub, Neal Lee (PI)
  • Spector, Arthur (PI)
  • Spector, Arthur (PI)
  • FIELD, JEFFREY (PI)
  • Chappell, David (PI)
  • Weintraub, Neal Lee (PI)
  • Spector, Arthur (PI)
  • FIELD, JEFFREY (PI)
  • Chappell, David (PI)
  • Knapp, Howard (PI)
  • Spector, Arthur A. (PI)
  • Field, F. Jeffrey (PI)
  • Chappell, David (PI)

Project: Research project

Project Details

Description

The overall objective is to determine how polyunsaturated fatty acids
(PUFA) influence cell properties and function. The current emphasis
concerns the relationship between PUFA, lipid peroxidation, and the
response of the intact cell to oxidative stress. Our goals are to identify
the cell lipids that are especially susceptible to oxidation, determine if
the PUFA content and composition can influence this process, and learn how
cells respond to PUFA products generated as a result of lipid peroxidation.
The work will be done with cultured cells, primarily the U937
monocyte/macrophage, but also with endothelial and vascular smooth muscle
cells. Lipid radical formation will be detected by electron spin resonance
(ESR) using spin traps such as alpha-[4]pyridyl 1-oxide]-N-tert-butyl
nitrone (POBN). Cultures will be supplemented during growth with n-3 and
n-6 PUFA to determine their influence on lipid radical formation. Using
this approach, we have detected a spin adduct formed by intact U937 cells
enriched with docosahexaenoic acid (DHA, 22:6n-3) in response to oxidative
stress. This opens up a new experimental approach to study lipid radical
formation by intact, functioning cells. There are five specific aims: (1)
Complete characterization of lipid radical formation by U937 cells
supplemented with DHA, including the cell lipids and organelles that are
involved, and the effectiveness of different reactive oxygen species in
initiating lipid peroxidation, (2) Determine whether other PUFA also
increase lipid radical formation by U937 cells, with emphasis on the
physiologically important n-3 and n-6 PUFA, (3) Determine the responses of
the intact cells to lipid peroxidation, characterize the lipid products
formed, and develop methods to protect the cells or minimize cell injury,
(4) Study the effects of PUFA on the responses of endothelial and smooth
muscle cells to oxidant stress, and (5) Test the effects of
hydroxyoctadienoic acids (HODEs), and determine how vascular cells process
these PUFA oxidation product. The results will provide new insight into
the effects of PUFA and their oxidation products on vascular function and
the atherogenetic process.
StatusFinished
Effective start/end date9/30/928/31/03

Funding

  • National Heart, Lung, and Blood Institute
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute

ASJC

  • Medicine(all)

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