W. Lieberthal et al., FATTY ACID-INDUCED CYTOTOXICITY - DIFFERENCES IN SUSCEPTIBILITY BETWEEN MDCK CELLS AND PRIMARY CULTURES OF PROXIMAL TUBULAR CELLS, The Journal of laboratory and clinical medicine, 129(2), 1997, pp. 260-265
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.