Manganese exposure to PC-12 cells alters triacylglycerol metabolism and promotes neurite outgrowth.

Exposure of PC-12 cells to MnCl2 (10-100 microM for 1 to 3 days) resulted in both morphological and metabolic changes as indicated by promotion of neurite outgrowth and an increased incorporation of labeled fatty acids (14:0, 18:1 and 20:4) into triacylglycerols (TG). Cells prelabeled with [14C]arachidonic acid (AA) showed a time-dependent decrease in labeled TG, and the rate of decline was inhibited by Mn (100 microM). In the pulse-chase type of study, the decrease in the proportion of labeled TG as well as labeled phosphatidylcholine (PC) was marked by an increase in labeled phosphatidylinositol and phosphatidylethanolamine. These results support previous notion that TG plays an important role in channeling the fatty acid nutrients for biosynthesis of membrane phospholipids. Thus, the Mn-induced inhibition of the ability to transfer TG fatty acids to other lipids in PC-12 cells may be an underlying cause for the observed morphological changes.