The Proposal: The release of arachidonic acid is involved in a myriad of mesangial cell functions, which have a profound impact on glomerular physiology and pathophysiologic processes. Phospholipase A2 (PLA2) is the dominant enzyme controlling arachidonic acid release in these cells, and is under stringent hormonal regulation. We have identified and characterized a novel, hormonally regulated form of PLA2 in rat renal mesangial cells. We have subsequently identified several distinct regulatory mechanisms which activate this enzyme, and have purified it to near homogeneity. We are proposing to elucidate the molecular mechanisms which regulate this important enzyme. Specifically, antibodies against the enzyme will be raised, and a cDNA clone will be isolated. These reagents will enable us to examine in detail, regulatory mechanisms suggested by our Preliminary Data. In addition, a clone for the enzyme will allow us to definitively determine the enzyme's role in mesangial cell function and examine structure function relationships.
| Gronich, J; Konieczkowski, M; Gelb, M H et al. (1994) Interleukin 1 alpha causes rapid activation of cytosolic phospholipase A2 by phosphorylation in rat mesangial cells. J Clin Invest 93:1224-33 |
| Schelling, J R; DeLuca, D J; Konieczkowski, M et al. (1994) Glucocorticoid uncoupling of antiogensin II-dependent phospholipase C activation in rat vascular smooth muscle cells. Kidney Int 46:675-82 |
