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Regulation of arachidonic acid metabolism in the perinatal brain during development and under ischemic stress
E Yavin1, B Kunievsky, N G Bazan
1Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Insights
Ischemia causes cell damage by altering lipids. This study shows phospholipase A2 and C enzymes generate key lipid messengers, arachidonic acid (AA) and diglycerides (DG), during oxygen deprivation in fetal rat brains.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Ischemia, or oxygen deprivation, leads to organ damage due to altered membrane permeability, ion flux, and energy depletion.
- Lipids like diglycerides (DG) and arachidonic acid (AA) increase during ischemia, but their role in cell death is unclear.
Purpose of the Study:
- To investigate the origin of lipid-derived second messengers during ischemia.
- To elucidate the fate of lipids following circulatory obstruction in a fetal rat brain model.
Main Methods:
- Fetal rat brains were prelabeled with [3H]arachidonic acid (AA).
- The study examined lipid changes after obstruction of the fetal-maternal circulation.
Main Results:
- Data suggest phospholipase A2 mediates the deacylation of poly-phosphoinositides (poly-PI) to produce free AA.
- Evidence indicates phospholipase C hydrolyzes phosphatidylcholine (PC) to generate DG during ischemic conditions.
Conclusions:
- Phospholipase A2 and C play a crucial role in generating lipid second messengers during ischemia.
- These lipid alterations are linked to cellular processes affected by oxygen deprivation, impacting cell function and survival.
Abstract:
Oxygen deprivation following cessation of blood flow to vital organs such as brain, heart, and kidney is a ubiquitous human disease, invariably leading to devastating consequences. Studies in experimental models support the contention that membrane permeability is altered, ion fluxes impaired, and energy stores depleted under these circumstances. Certain lipids such as diglycerides (DG) and arachidonic acid (AA), both of which are important cellular second messengers, appear to increase during ischemia. At this point, the contribution of these and other lipids to cell deregulation, loss of function, and ultimate death has not been clarified because no precise link between lipid alterations as detected in ischemia and subsequent cellular processes has been made. In this report we examine the origin of lipid-derived second messengers in fetal rat brain prelabeled with [3H]AA and study the fate of various lipids upon obstruction of the fetal-maternal circulation. The data support the possibility of a phospholipase A2-mediated deacylation of poly-phosphoinositides (poly-PI) to form free AA and a phospholipase C-mediated hydrolysis of PC to form DG during ischemia.