Changes of polyphosphoinositides, lysophospholipid, and free fatty acids in transient cerebral ischemia of rat brain

Abstract

Phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4, 5-bisphosphate (PIP2), 1, 2-diglyceride (DG), lysophosphatidylcholine (LPC), and free fatty acids (FFA) contents, as well as their fatty acid composition, were measured in transient global cerebral ischemia. ATP and CTP were also studied. Male Wistar rats were subjected to 1, 5, and 30 min of ischemia and 10, 30, and 60 min of recirculation following 30 min of ischemia. In addition, for the quantification of PI, PIP, and PIP2, rats were also subjected to 30 and 60 min of recirculation following 5 min of ischemia. PIP2 and PIP decreased rapidly during 5 min of ischemia and recovered completely after recirculation. DG increased almost at the same rate during ischemia and returned to normal after recirculation. PI showed almost no changes throughout entire course. LPC increased during 5 min of ischemia and returned to normal after recirculation. Stearic acid and arachidonic acid contained in DG increased during 5 min of ischemia, whereas saturated fatty acids increased in LPC. Among the FFA accumulated during ischemia, stearic acid and arachidonic acid increased rapidly and were followed by increases of other FFA. From these results, the pathways for the increase of FFA during ischemia and the fate of FFA after recirculation are discussed. In addition, the importance of the changes of PIP, PIP2, and LPC is also discussed.

Lysophosphatidylcholine induces glial cell activation: Role of rho kinase

“…Examples include increased LPC in plasma of multiple sclerosis patients (Andreoli et al, 1973) and in white matter of aged human brain exhibiting senile atrophy of Alzheimer type (Wender et al, 1988). LPC levels have been reported to be significantly increased in a rat model of cerebral ischemia (Kinouchi et al, 1990). Overall, the findings suggest that, as a metabolite of PLA 2 and as a proinflammatory phospholipid, LPC could play a significant role in the pathogenesis of neurological disorders by modulating neuroinflammatory responses.…”

Lysophosphatidylcholine Stimulates IL-1β Release from Microglia via a P2X7 Receptor-Independent Mechanism

“…Increased LPC concentrations of up to 200 M were detected in the brain following ischemia (26,27), epilepsy (28), and inflammation (29). Under pathological conditions, overstimulation of phospholipase A 2 results in breakdown of membrane phosphatidylcholine and subsequent accumulation of LPC in the damaged tissue.…”

Molecular Mechanisms Underlying Neuroprotective Effects of Albumin After Ischemic Stroke

“…However, free fatty acids have a higher affinity to albumin than lysoPC, and fatty acids effectively displace lysoPC from albumin. 7 Thus, in acute ischemic conditions, when the levels of both lysoPC and free fatty acids increase, 8 the binding capacity of endogenous albumin for lysoPC may become saturated. Therefore, one of the protective mechanisms exerted by high-dose albumin infusion in ischemic stroke may be scavenging of the accumulating lysoPC and preventing its proinflammatory and proapoptotic effects.…”