Fuller B B
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Pigment Cell Res. 1987;1(3):176-80. doi: 10.1111/j.1600-0749.1987.tb00410.x.
Calcium ionophore A23187 lowers basal levels of tyrosinase and inhibits the MSH-induced increase in tyrosinase in Cloudman S-91 mouse melanoma cell cultures. Ionophore at a concentration of 10(-6) g/ml causes a 50% reduction in basal levels of tyrosinase and inhibits the MSH stimulated level of enzyme. Ionophore A23187 also inhibits the PGE1 mediated stimulation of tyrosinase, as well as the rise in enzyme activity observed in cells exposed to either theophylline (1 mM) or dbcAMP (10(-4)M). Ionophore does not affect basal levels of cyclic AMP nor the elevated levels produced by either MSH or PGE1, suggesting then, that the antagonistic activity of A23187 is localized to a point in the pathway of tyrosinase activation distal to the formation of cAMP. Ionophore causes a rapid and marked (greater than 50%) inhibition of cellular protein synthesis and it is possible that this calcium mobilizing compound may exert its inhibitory effects on tyrosinase activity by causing a general reduction in cellular translation. Since the inhibition of protein synthesis occurs in cells exposed to ionophore in either the presence or absence of calcium in the medium, it seems, likely that the ionophore may exert its effects by causing the release of calcium from intracellular sites.
钙离子载体A23187可降低酪氨酸酶的基础水平，并抑制促黑素（MSH）诱导的Cloudman S - 91小鼠黑色素瘤细胞培养物中酪氨酸酶水平的升高。浓度为10(-6) g/ml的离子载体可使酪氨酸酶的基础水平降低50%，并抑制MSH刺激的酶水平。离子载体A23187还可抑制前列腺素E1（PGE1）介导的酪氨酸酶刺激作用，以及在暴露于茶碱（1 mM）或二丁酰环磷腺苷（dbcAMP，10(-4)M）的细胞中观察到的酶活性升高。离子载体不影响环磷酸腺苷（cAMP）的基础水平，也不影响由MSH或PGE1产生的升高水平，因此表明，A23187的拮抗活性定位于cAMP形成远端的酪氨酸酶激活途径中的某一点。离子载体可迅速且显著（超过50%）地抑制细胞蛋白质合成，并且这种钙动员化合物可能通过导致细胞翻译普遍减少而对酪氨酸酶活性发挥其抑制作用。由于在培养基中存在或不存在钙的情况下，暴露于离子载体的细胞中都会发生蛋白质合成的抑制，因此，离子载体似乎可能通过引起细胞内钙的释放来发挥其作用。
