Marine lipids recently have been receiving prominent attention for their capacity to prevent atherosclerosis, and thus are being recommended to the population as dietary supplements. However, little is known about the susceptibility of membranes incorporated with marine lipids to an ischemic or anoxic insult. The general goal of this proposal is to understand the mechanisms by which membrane incorporation of marine lipids can accentuate anoxic cellular injury, leading to cell dealth. Marine lipid-incorporated cells with exposure to anoxia will be assessed fro enhanced oxygen free radical activity compared to beef tallow-incorporated cells, by using a recently developed intracellular fluorescent probe. Mitochondrial function in situ in anoxic cells will be evaluated in marine lipid compared to beef tallow-incorporated cells. With exposure to anoxia, we shall assess mitochondrial cardiolipin (the phospholipid essential to the catalytic function of site I of the electron transport chain) and lysocardiolipin content to determine whether marine lipid compared to beef tallow- incorporated membranes are maore susceptible to calcium- activated phospholipase A2 degradation, occurring with anoxia. By using dibucaine, a phospholipase A2 inhibitor, we will determine whether calcium-activated phospholipase A2 through its degradation of cardiolipin is of primary importance in producing the site I defect with anoxia. Lastly, by assessing cell viability and growth on defined recovery media with site I or site II substrates post anoxia, the implications of mitochondrial site I injury will be investigated to determine if this represents the fundamental cause of cell death associated with anoxia and reoxygenation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK001320-05
Application #
3080430
Study Section
Diabetes and Digestive and Kidney Diseases Special Grants Review Committee (DDK)
Project Start
1984-07-01
Project End
1990-05-31
Budget Start
1989-05-01
Budget End
1990-05-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199