Lysophosphatidic acid-induced calcium mobilization and proliferation in kidney proximal tubular cells

Dixon, Richard J., Ken Young, and Nigel J. Brunskill. Lysophosphatidic acid -induced calcium mobilization and proliferation in kidney proximal tubular cells. Am. J. Physiol. 276 (Renal Physiol. 45): F191-F198, 1999. -Patients with proteinuria tend to develop progressive renal disease with proximal tu bular cell atrophy and interstitial scarring. It has been suggested that th e nephrotoxicity of albuminuric states may be due to the protein molecule i tself or by lipids, such as lysophosphatidic acid (LPA), that albumin carri es. LPA was found to cause a transient increase in intracytoplasmic free Ca 2+ ([Ca2+](i)) in opossum kidney proximal tubule cells (OK) that was maxima l at 100 mu M LPA and was dose dependent with an EC50 of 2.6 x 10(-6) M. Th is Ca2+ mobilization was from both internal stores and across the plasma me mbrane and was pertussis toxin (PTX) insensitive. Treatment of OK cells wit h 100 mu M LPA for 5 min was found to cause a twofold increase in [H-3]thym idine incorporation and a three- to fivefold increase over control after 24 h. This was highly PTX sensitive and insensitive to pretreatment with the tyrosine kinase inhibitors genistein and herbimycin A. These findings may b e of significance in the progression of renal disease and indicate the pote ntial importance of lipids in modulating proximal tubule cell function and growth.