Schöfl C, Sanchez-Bueno A, Dixon C J, Woods N M, Lee J A, Cuthbertson K S, Cobbold P H, Birchall J D
Department of Human Anatomy and Cell Biology, University of Liverpool, U.K.
Biochem J. 1990 Jul 15;269(2):547-50. doi: 10.1042/bj2690547.
Aluminium is known to be toxic to cells from bone, brain and bone marrow but the molecular target(s) affected by Al3+ are not known. We show here that Al3+ disrupts the oscillatory free Ca2+ responses of hepatocytes exposed to the Ca2(+)-mobilizing agonist phenylephrine. Al3+ initially increases the frequency of the oscillations and later induces broad Ca2+ spikes lasting several minutes. These broad spikes persist after removal of both agonist and Al3+ from the medium. In the absence of agonist, Al3+ has no effect on free Ca2+. The data suggest that some component(s) of the receptor-phosphoinositide-Ca2+ signalling pathway might be the site at which Al3+ exerts toxic effects.
已知铝对来自骨骼、大脑和骨髓的细胞具有毒性,但尚不清楚受Al3+影响的分子靶点。我们在此表明,Al3+会破坏暴露于钙离子动员激动剂去氧肾上腺素的肝细胞的振荡性游离钙离子反应。Al3+最初会增加振荡频率,随后诱导持续数分钟的广泛钙离子尖峰。在从培养基中去除激动剂和Al3+后,这些广泛的尖峰仍然存在。在没有激动剂的情况下,Al3+对游离钙离子没有影响。数据表明,受体-磷酸肌醇-钙离子信号通路的某些成分可能是Al3+发挥毒性作用的位点。