DCP-LA-phosphatidylinositol and its enantiomer exhibit different bioactivities

The present study was conducted to understand biochemical and biological characteristics of the phosphatidylinositol (PI) derivative 1,2-O-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-Sn-glycero-3-phosphatidyl-D-1-inositol (diDCP-LA-PI) and its enantiomer 1,2-O-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-Sn-glycero-3-phosphatidyl-L-1-inositol (diDCP-LA-PIe), with 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) on the α and β position.

Activities of protein kinase C (PKC) and protein phosphatases such as protein phosphatase 1 (PP1), PP2A, and protein tyrosine phosphatase 1B (PTP1B) were assayed under the cell-free conditions and in PC-12 cells. Akt1/2 activity was monitored by quantifying phosphorylation at Thr308/309 and Ser473/474 in PC-12 cells.

diDCP-LA-PI significantly activated PKCα, -βΙ, -δ, and -ε, to an extent greater than that for diDCP-LA-PIe. diDCP-LA-PI still activated PKC in PC-12 cells, with the potential higher than that for diDCP-LA-PIe. Both diDCP-LA-PI and diDCP-LA-PIe reduced PP1 activity to a similar extent (30% of basal levels). diDCP-LA-PI enhanced PP2A activity to 180% of basal levels, while diDCP-LA-PIe had no effect. Drastic inhibition of PTP1B was obtained with diDCP-LA-PI and diDCP-LA-PIe, the extent reaching nearly 0% of basal levels. diDCP-LA-PI and diDCP-LA-PIe increased phosphorylation of Akt1/2 at Thr308/309 and Ser473/474 in PC-12 cells in the presence and absence of the PP2A inhibitor okadaic acid, respectively.

The results of the present study show that diDCP-LA-PI and diDCP-LA-PIe exhibit different bioactivities with the different potentials each other.