Phosphatidic acid is the prominent product of endogenous neuronal nuclear lipid phosphorylation, an activity enhanced by sphingosine, linked to phospholipase C and associated with the nuclear envelope

Abstract

Using endogenous lipid substrates, assays of lipid phosphorylation indicated that neuronal nuclei had a considerable superiority in phosphatidic acid (PA) formation when compared with homogenates and other subfractions of cerebral cortex. This predominance of neuronal nuclear PA labelling was linked to a sizable pool of nuclear diacylglycerols that expanded significantly with incubation. PA was also the dominant product of neuronal nuclear lipid phosphorylation reactions. Nuclear envelope preparations and the parent neuronal nuclei showed specific rates of PA formation that were comparable, based upon membrane phospholipid contents. As well, using an exogenous diacylglycerol substrate, the distribution of diacylglycerol kinase activities closely followed phospholipid contents of subfractions derived from the neuronal nucleus during envelope preparation. This evidence suggested an association between diacylglycerol kinase and the neuronal nuclear envelope. Nuclear PA formation increased in the presence of sphingosine, while sphingosine decreased PA formation in other subfractions. Likely sphingosine exerted its effect on nuclear diacylglycerol kinase, as sphingosine did not elevate levels of nuclear diacylglycerols. Phosphoinositidase C was present in the nuclei and inhibitors of this enzyme did decrease PA formation, indicating diacylglycerols from inositides as substrates for nuclear diacylglycerol kinase. The nuclear envelope fraction had a considerably lower specific phosphoinositidase C activity than the parent nuclei, and showed an activation of PA formation by sphingosine, but a less efficient handling of the exogenous diacylglycerol substrate. It is possible that phosphoinositidase C and diacylglycerol kinase are closely situated within the neuronal nuclei, and a loss of the former activity may compromise the latter.