Basal phosphatidylinositol turnover controls aortic Na+/K+ ATPase activity.

Abstract

To determine whether basal phosphoinositide turnover plays a role in metabolic regulation in resting rabbit aortic intima-media incubated under steady state conditions, we used deprivation of extracellular myo-inositol as a potential means of inhibiting basal phosphatidylinositol (PI) synthesis at restricted sites and of depleting small phosphoinositide pools with a rapid basal turnover. Medium myo-inositol in a normal plasma level was required to prevent inhibition of a specific component of basal de novo PI synthesis that is necessary to demonstrate a discrete rapidly turning-over 11,3-'4Clglycerol-labeled PI pool. Medium myoinositol was also required to label the discrete PI pool with [1-'4Clarachidonic acid (AA). The rapid basal turnover of this PI pool, when labeled with glycerol or AA, was not attributable to its utilization for polyphosphoinositide formation, and it seems to reflect basal PI hydrolysis. Depleting endogenous free AA with medium defatted albumin selectively inhibits the component of basal de novo PI synthesis that replenishes the rapidly turningover PI pool. A component of normal resting energy utilization in aortic intima-media also specifically requires medium myoinositol in a normal plasma level and a free AA pool; its magntude is unaltered by indomethacin, nordihydroguaiaretic acid, or Ca2+-free medium. This energy utilization results primarily from Na+/ K+ ATPase activity (ouabain-inhibitable 02 consumption), and in Ca2+-free medium deprivation of medium myo-inositol or of free AA inhibits resting Na+/K+ ATPase activity to a similar degree (60%, 52%). In aortic intima-media basal PI turnover controls a major fraction of resting Na+/K+ ATPase activity.

Differential regulation of protein kinase C and (Na,K)-adenosine triphosphatase activities by elevated glucose levels in retinal capillary endothelial cells.

“…In addition, similar findings of elevated glucose on PKC activities in isolated rat renal glomeruli were reported at the National Meeting of the American Federation of Clinical Research in May, 1988May, (1988 tein kinase C (PKC)' and (Na,K)-ATPase (3,4). The activities of these two enzymes may be altered by the elevation of glucose levels in cells via the increase of intracellular sorbitol levels due to the activity of aldose reductase (3,4), and may secondarily affect myoinositol levels by inhibiting its uptake (4)(5)(6). Myoinositol is a substrate for the production of phosphoinositides (PI) and their breakdown products, inositol phosphates (InsPs) and diacylglycerol (DAG), which are regulators of cytosolic calcium and PKC, respectively.…”

“…The steady-state levels of IPs did not change with the conditions under which PKC activities were measured. However, InsP turnover and DAG levels need to be determined before conclusions can be drawn (3,8,9). Besides affecting PKC translocation directly, glucose levels may also indirectly affect PKC and PI metabolism by lowering cellular myoinositol levels due to the inhibition of its uptake caused either by elevation of glucose or sorbitol levels (4-6 Effect of PMA on PKC activity of endothelial cells.…”

Endothelium-dependent inhibition of Na(+)-K+ ATPase activity in rabbit aorta by hyperglycemia. Possible role of endothelium-derived nitric oxide.

“…Aortas incubated under these conditions for up to ( 14). In addition, we have found that their rate ofoxygen consumption (6.1 Amol/ mg wet wt per h; n = 2;) is identical to that reported for rabbit thoracic aorta by Chace and Odessey ( 14) and Simmons and co-workers ( 15).…”

CDP-diacylglycerol synthetase-controlled phosphoinositide availability limits VEGFA signaling and vascular morphogenesis

“…53 Increased turnover or production of phosphoinositides, especially PIP2, has been observed in several different types of cells under physiologic or cellular signaling stimulation. [54][55][56][57][58] We would hypothesize that endothelial cells have elevated downstream PIP2-dependent ERK activation and greater PIP2 consumption than other cell types, at least during development. Greater PIP2 consumption would necessitate more active resynthesis of this substrate, making the endothelium more sensitive to deficits in PIP2 resynthesis.…”