Propanil-Induced Ca2^+ Entry and Apoptosis in MDCK Canine Renal Tubular Cells

Abstract

Propanil is an herbicide used primarily in rice and wheat production. Propanil poisoning can produce methemoglobinemia, tissue hypoxia, and depression of the central nervous system and the respiratory system. However, the nephrotoxic potential of propanil has not been examined in detail. This study explored the effect of propanil on [Ca^(2+)]i, viability and apoptosis in MDCK canine renal tubular cells. At concentrations between 50-100 μM, propanil induced a [Ca^(2+)]i rise. This Ca^(2+) signal disappeared when extracellular Ca^(2+) was removed, and was not altered by pre-addition of nifedipine, econazole, SKF96365, phorbol myristate acetate (PMA), and GF109203X. At concentrations between 10 and 40 μM, propanil killed cells in a concentration-dependent manner. The cytotoxic effect of propanil was not reversed by prechelating cytosolic Ca^(2+) with an acetoxy-methyl ester of 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid acetoxy methyl (BAPTA/AM). Annexin V/propidium iodide staining data suggest that propanil induced apoptosis in a concentrationdependent manner. Together, in MDCK renal tubular cells, propanil induced Ca^(2+) entry via non-store-operated Ca^(2+) pathways. Propanil also evoked cell death that might involve apoptosis in a Ca^(2+)-independent manner.