FATTY ACID-INDUCED CYTOTOXICITY - DIFFERENCES IN SUSCEPTIBILITY BETWEEN MDCK CELLS AND PRIMARY CULTURES OF PROXIMAL TUBULAR CELLS

We have compared the cytotoxicity of exogenously added fatty acid (ole ic acid) and that of endogenous free fatty adds released from cell mem branes by phospholipase A(2) in primary cultures of mouse proximal tub ular (MPT) cells and in Madine-Darby canine kidney (MDCK) cells. Expos ure of MPT cell monolayers to oleic acid (125 mmol/L) for 2 hours resu lted in severe irreversible injury to 70% +/- 4% of MPT cells. In stri king contrast, only 8% +/- 3% of MDCK cells were killed by the same in sult, This striking difference in the response to exogenous oleate by MPT and MDCK cells was associated with modest and comparable reduction s in cell adenosine triphosphate (ATP) content in both cell types. Che mical anoxia induced by cyanide plus deoxyglucose (CN-DOG) in the abse nce of glucose was associated with greater injury in MPT cells (45% +/ - 6% killed) than in MDCK cells (16% +/- 5% cells killed) despite seve re and comparable depletion of cell ATP content in both MPT cells (96. 0% +/- 0.6% reduction) and MDCK cells (96.0% +/- 0.5% reduction), The release of endogenous fatty acids by the exposure of cells to exogenou s phospholipase A(2) caused mild injury in both cell types that was mo re severe in MPT cells than in MDCK cells. The combined insult of phos pholipase A(2) and chemical anoxia for 2 hours caused substantially gr eater cell injury in both MPT and MDCK cells than either intervention alone, but the combined insult was still more damaging to MPT cells (7 3% +/- 4% killed) than to MDCK cells (30% +/- 4% kilted). We conclude that the cell membrane in MDCK cells is intrinsically more resistant t o fatty acid-induced injury than the lipid membrane in MPT cells.