Naproxen is an anti-inflammatory drug that affects cellular calcium ion (Ca2+) homeostasis and viability in different cells. This study explored the effect of naproxen on [Ca2+]i and viability in Madin-Darby canine kidney cells (MDCK) canine renal tubular cells. At concentrations between 50 μM and 300 μM, naproxen induced [Ca2+]i rises in a concentration-dependent manner. This Ca2+ signal was reduced partly when extracellular Ca2+ was removed. The Ca2+ signal was inhibited by a Ca2+ channel blocker nifedipine but not by store-operated Ca2+ channel inhibitors (econazole and SKF96365), a protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, and a PKC inhibitor GF109203X. In Ca2+-free medium, pretreatment with 2,5-di-tert-butylhydroquinone or thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ pumps, partly inhibited naproxen-induced Ca2+ signal. Inhibition of phospholipase C with U73122 did not alter naproxen-evoked [Ca2+]i rises. At concentrations between 15 μM and 30 μM, naproxen killed cells in a concentration-dependent manner, which was not reversed by prechelating cytosolic Ca2+ with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid acetoxymethyl. Annexin V/propidium iodide staining data suggest that naproxen induced apoptosis. Together, in MDCK renal tubular cells, naproxen induced [Ca2+]i rises by inducing Ca2+ release from multiple stores that included the endoplasmic reticulum and Ca2+ entry via nifedipine-sensitive Ca2+ channels. Naproxen induced cell death that involved apoptosis.
Prostaglandin E1 attenuates high glucose-induced apoptosis in proximal renal tubular cells by inhibiting the JNK/Bim pathway
