Effect of thimerosal on Ca2+ movement and viability in human oral cancer cells
The effect of thimerosal on cytosolic free Ca2+ concentrations ([Ca2+]i) in human oral cancer cells (OC2) is unclear. This study explored whether thimerosal changed basal [Ca2+]i levels in suspended OC2 cells by using fura-2. Thimerosal at concentrations between 1-50£gM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. Thimerosal-induced Ca2+ influx was not blocked by L-type Ca2+ entry inhibitors and protein kinase C modulators [phorbol 12-myristate 13-acetate (PMA) and GF109203X]. In Ca2+-free medium, 50£gM thimerosal failed to induce a [Ca2+]i rise after pretreatment with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Inhibition of phospholipase C with U73122 did not change thimerosal-induced [Ca2+]i rises. At concentrations between 5 and 10£gM thimerosal killed cells in a concentration-dependent manner. The cytotoxic effect of 8£gM thimerosal was potentiated by prechelating cytosolic Ca2+ with the Ca2+ chelator BAPTA/AM. Flow cytometry data suggested that 1-7£gM thimerosal induced apoptosis in a concentration-dependent manner. Collectively, in OC2 cells, thimerosal induced [Ca2+]i rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via non-L-type Ca2+ channels. Thimerosal killed cells in a concentration-dependent manner via apoptosis.
Advisor:Chen-Chih Kao; Chung-Ren Jan; Chen-Fu Thiao
School:National Sun Yat-Sen University
School Location:China - Taiwan
Source Type:Master's Thesis
Keywords:oral cells oc2 apoptosis ca2 thimerosal
Date of Publication:02/04/2009