Control of cell proliferation and mitochondrial activity by regulators of chloride ion transport in renal epithelial A6 cells

Abstract

Recent studies show that transepithelial ion transport plays an important role in fundamental cellular functions such as cell proliferation and cell death. Particularly, chloride ion transport is reported to affect cell proliferation by regulating cell volume. In addition, mitochondria which have an extremely important role as energy-producing organella are known to be influenced by intracellular ion environments. In the present study, we studied whether chloride ion transport regulates cell proliferation and activity of mitochondria in renal epithelial A6 cells by using regulators of chloride ion channel and Na+/K+/2Cl- cotransporter (NKCC). The cell proliferation was examined by MTS assay and direct cell count. The activity of mitochondria was measured by fluorescent coloring with mito-Red. Treatment with NPPB (a chloride ion channel blocker) and quercetin (an NKCC regulator) inhibited cell growth and activity of mitochondria, but bumetanide (an NKCC inhibitor) did not affect them. Based on these results, it is suggested that regulators of chloride ion transport would influence cell proliferation and mitochondrial activity by regulating intracellular ion environments. Supported by JSPS 15659052 (YM), 15590189 (NN), 15790120 (HM), 15591427 (HI). [Jpn J Physiol 54 Suppl:S81 (2004)]