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Maprotiline‐induced Ca2+ fluxes and apoptosis in human osteosarcoma cells
Authors:Wei‐Chuan Liao  Chorng‐Chih Huang  Yih‐Chau Lu  Chao‐Chuan Chi  Sau‐Tung Chu  Hsing‐Hao Su  Chun‐Chi Kuo  Jin‐Shiung Cheng  Li‐Ling Tseng  Chin‐Man Ho  Chung‐Ren Jan
Abstract:The effect of maprotiline on cytosolic free Ca2+ concentrations ([Ca2+]i) and cell viability was explored in human osteosarcoma cells (MG63), using the fluorescent dyes fura‐2 and WST‐1, respectively. Maprotiline at concentrations of ≥20 µM increased [Ca2+]i in a concentration‐dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. The maprotiline‐induced Ca2+ influx was sensitive to inhibition by aristolochic acid (a phospholipase A2 inhibitor). In Ca2+‐free medium, after treatment with 1 µM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 200 µM maprotiline failed to induce a [Ca2+]i rise. At concentrations of 50–100 µM maprotiline killed cells in a concentration‐dependent manner. The cytotoxic effect of 60 µM maprotiline was slightly enhanced by prechelating cytosolic Ca2+ with 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid (BAPTA). Propidium iodide staining data suggested that maprotiline induced apoptosis between concentrations of 60–70 µM, which was enhanced by BAPTA. Collectively, in MG63 cells, maprotiline induced [Ca2+]i rises by causing Ca2+ release from the endoplasmic reticulum and Ca2+ influx from phospholipase A2‐regulated Ca2+ channels. Furthermore, maprotiline caused apoptosis that was regulated by Ca2+. Drug Dev Res 71: 268–274, 2010. © 2010 Wiley‐Liss, Inc.
Keywords:apoptosis  Ca2+  maprotiline  MG63 cells  osteosarcoma cells
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