Sphingosine-1-phosphate (SPP) is a unique sphingolipid metabolite involved in cell growth regulation and signal transduction. SPP is formed from sphingosine in cells by the action of sphingosine kinase, an enzyme whose activity can be stimulated by growth factors. Little is known of the mechanisms by which sphingosine kinase is regulated. We found that acidic phospholipids, particularly phosphatidylserine, induced a dose-dependent increase in sphingosine kinase activity due to an increase in the apparent Vmax of the enzyme. Other acidic phospholipids, such as phosphatidylinositol, phosphatidic acid, phosphatidylinositol bisphosphate, and cardiolipin stimulated sphingosine kinase activity to a lesser extent than phosphatidylserine, whereas neutral phospholipids had no effect. Diacylglycerol, a structurally similar molecule which differs from phosphatidic acid in the absence of the phosphate group, failed to induce any changes in sphingosine kinase activity. Our results suggest that the presence of negative charges on the lipid molecules is important for the potentiation of sphingosine kinase activity, but the effect does not directly correlate with the number of negative charges. These results also support the notion that the polar group confers specificity in the stimulation of sphingosine kinase by acidic glycerophospholipids. The presence of a fatty acid chain in position 2 of the glycerol backbone was not critical since lysophosphatidylserine also stimulated sphingosine kinase, although it was somewhat less potent. Dioleoylphosphatidylserine was the most potent species, including a fourfold stimulation, whereas distearoyl phosphatidylserine was completely inactive. Thus, the degree of saturation of the fatty acid chain of the phospholipids may also play a role in the activation of sphingosine kinase.

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in infants with coarctation of the aorta. J Thorac Vase Surg 81: [323][324][325] 1981 8. Liberfhson RR: Congenital Heart Disease in the Child, Adolescent and Adult Patient. In: The Practice of Cardiology, Johnson RA, Haber E, Austin WG (eds.) Boston, Little Brown, 1980, pp. 760-761 during 30 minutes of recirculation. They also observed a marked (3-fold) increase in the relative content of arachidonic acid. During the recirculation period following ischemia the neurophysiological and metabolic functions might be restored if no irreversible cell damage occurred. A prerequisite for recovery is an adequate perfusion, whereas immediate or delayed perfusion defects might be the cause for irreversibility of brain function.14 ' I5Hossmann 16 reviewed various factors that may contribute to delayed hypoperfusion thus increasing the primary ischemic region. Among these factors are blood coagulation and vascular spasm.The maintenance of normal tissue perfusion depends on a balanced interaction of two prostaglandins which have opposite effects at the blood-endothelial interface, namely thromboxane A 2 (TXA 2 ) and prostaglandin I 2 (PGI 2 ). 17 ' 18 Both prostaglandins have the same precursor, cyclic-endoperoxide (PGH 2 ), but while TXA 2 is a potent platelet aggregator and vasoconstrictor, 19 PGI 2 inhibits platelet aggregation and is a vasodilator. 20 Thus, any interruption in the balanced production of these compounds which might result in an increase of TXA 2 could diminish local blood flow. Hallenbeck and Furlow 21 have shown that dogs exposed to complete ischemia had low post ischemic blood flow with focal zones of greatly impaired reperfusion. A significant increase in the blood flow during the post ischemic period was observed in animals receiving either indomethacin prior to ischemia or a combination of indomethacin and PGI 2 after ischemia. Gaudet and Levine have demonstrated that gerbils pre- The Effect of Incomplete Cerebral Ischemia on Prostaglandin Levels in Rat BrainE, SHOHAMI, PH.D., J. ROSENTHAL, M.SC, AND S. LAW, M.D.* SUMMARY Rats were subjected to severe incomplete cerebral ischemia followed by recirculation. The levels of several of the cyclooxygenase products of arachidonic acid were measured at 5 and 15 minutes of ischemia and at 30 minutes of recirculation following 15 minutes of ischemia, PGE 2 accumulated during the first 5 min. of ischemia and its level declined at 15 min. and returned to control level at 30 min. of recirculation. TXB 2 , on the other hand, increased during the whole time course of the experiment and at the end of the post ischemic period its level was 5 times higher than control. Treatment of the animals with indomethacin (4 mg/Kg, i.v.) prior to ischemia reduced the levels of these products without altering the pattern of their changes. During the ischemic period the EEG was isoelectric and the mean recovery time of electrical cortical activity after 15 min. of ischemia was 10.4 ± 3.5 min. in the control rats. The rats which received indomethacin recovered faster (4.3 ± 0....

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