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• W2014039069 abstract "In this study, we investigated ionic mechanisms involved in growth arrest induced by extracellular ATP in androgen-independent prostate cancer cells. Extracellular ATP reversibly induced a rapid and sustained intracellular pH (pH(i)) decrease from 7.41 to 7.11. Inhibition of Ca(2+) influx, lowering extracellular Ca(2+), and buffering cytoplasmic Ca(2+) inhibited ATP-induced acidification, thereby demonstrating that acidification is a consequence of Ca(2+) entry. We show that ATP induced reuptake of Ca(2+) by the mitochondria and a transient depolarization of the inner mitochondrial membrane. ATP-induced acidification was reduced after the dissipation of the mitochondrial proton gradient by rotenone and carbonyl cyanide p-trifluoromethoxyphenylhydrazone, after inhibition of Ca(2+) uptake into the mitochondria by ruthenium red, and after inhibition of the F(0)F(1)-ATPase with oligomycin. ATP-induced acidification was not induced by either stimulation of the Cl(-)/HCO(3)(-) exchanger or inhibition of the Na(+)/H(+) exchanger. In addition, intracellular acidification, induced by an ammonium prepulse method, reduced the amount of releasable Ca(2+) from the endoplasmic reticulum, assessed by measuring change in cytosolic Ca(2+) induced by thapsigargin or ATP in a Ca(2+)-free medium. This latter finding reveals cross talk between pH(i) and Ca(2+) homeostasis in which the Ca(2+)-induced intracellular acidification can in turn regulate the amount of Ca(2+) that can be released from the endoplasmic reticulum. Furthermore, pH(i) decrease was capable of reducing cell growth. Taken together, our results suggest that ATP-induced acidification in DU-145 cells results from specific effect of mitochondrial function and is one of the major mechanisms leading to growth arrest induced by ATP." @default.
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• W2014039069 date "2004-12-01" @default.
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• W2014039069 title "The role of intracellular pH in cell growth arrest induced by ATP" @default.
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• W2014039069 doi "https://doi.org/10.1152/ajpcell.00578.2003" @default.
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