Modulation by cytosol and commercial proteins of acid-active phospholipase A2 from adrenal medulla.

Expression of soluble, acid-active phospholipase A2 from a granule-enriched fraction of bovine adrenal medulla is modulated by adrenal medullary cytosol in an ionic strength- and pH-dependent manner. At 150 nM Na+, cytosol is inhibitory in a dose-dependent manner while at 14 and 50 mM Na+ inhibition is preceded by stimulation. The extent of inhibition increases with increasing Na+ while the extent of stimulation increases with decreasing Na+. Effects are seen primarily below pH 5. Bovine liver cytosol behaves similarly, and soluble, acid-active phospholipases A2 from bovine and rat liver are also modulated by cytosol. The predominant regulatory component has a molecular weight of 67 000 as determined by gel permeation chromatography. Serum albumin and other commercially available proteins affect expression of acid-active phospholipase A2 in a manner similar to cytosol. Acid-active phospholipase A2 activity is also present in cytosol, it is enhanced substantially upon precipitation of cytosolic proteins, and is subsequently suppressed by added protein. Modulatory effects of cytosol result from its interaction with substrate, not enzyme, but are not due to dilution of substrate by cytosolic phospholipids. The study demonstrates that proteins modulate expression of acid-active phospholipases A2 by interacting with substrate in an ionic strength- and pH-dependent fashion. Such interactions may be important in the in vivo regulation of acid-active phospholipases A2.