Oxidation by thimerosal increases calcium levels in renal tubular cells

The effect of thimerosal, a reactive oxidant, on cytoplasmic free Ca ²⁺ concentrations ([Ca²⁺]_i) in Madin Darby canine kidney (MDCK) cells was explored by using the Ca²⁺-sensitive dye fura-2. Thimerosal acted in a concentration-dependent manner with an EC ₅₀ of 0.5 μM. The Ca²⁺ signal comprised a gradual rise and a sustained elevation. Removal of extracellular Ca²⁺ reduced 80% of the signal. In Ca²⁺-free medium, the [Ca²⁺] _i rise induced by 1 μM thapsigargin (an endoplasmic reticulum Ca²⁺ pump inhibitor) was completely inhibited by pretreatment with 5 μM thimerosal. The thimerosal (5 μM)-induced Ca²⁺ release was not changed by inhibition of phospholipase C with 2 μM U73122. Collectively, this study shows that thimerosal induced [Ca²⁺]_i rises in renal tubular cells via releasing store Ca²⁺ from the endoplasmic reticulum Ca²⁺ stores in a manner independent of phospholipase C activity.