Kiuchi K, Hagiwara M, Hidaka H, Nagatsu T
Department of Biochemistry, Nagoya University School of Medicine, Japan.
Neurosci Lett. 1988 Jun 29;89(2):209-15. doi: 10.1016/0304-3940(88)90383-7.
Effects of the 1-methyl-4-phenylpyridinium ion (MPP+) on DOPA formation and phosphorylation of tyrosine hydroxylase (TH) of rat pheochromocytoma PC12h cells were examined after the cells were cultured with MPP+. DOPA formed from endogenous tyrosine in PC12h cells after a 3-day culture with 100 microM MPP+ was decreased to less than 50% as compared to that in the control cells cultured without MPP+. Kinetical study showed that two apparent forms of TH with different Km existed in the cells cultured with 100 microM MPP+ but one form in that of control. Incorporation of radioactive phosphate into TH molecule was also reduced to 50% of its control value following a 3-day exposure to 100 microM MPP+. These results suggest that MPP+ acutely inhibits the phosphorylation of TH to decrease cellular DOPA formation.
在用1-甲基-4-苯基吡啶离子(MPP+)培养大鼠嗜铬细胞瘤PC12h细胞后,检测了MPP+对PC12h细胞中多巴(DOPA)形成及酪氨酸羟化酶(TH)磷酸化的影响。与未用MPP+培养的对照细胞相比,用100微摩尔MPP+培养3天后,PC12h细胞内由内源性酪氨酸生成的DOPA减少至不到对照细胞的50%。动力学研究表明,用100微摩尔MPP+培养的细胞中存在两种具有不同米氏常数(Km)的明显的TH形式,而对照细胞中只有一种形式。在暴露于100微摩尔MPP+ 3天后,TH分子中放射性磷酸盐的掺入也降至对照值的50%。这些结果表明,MPP+急性抑制TH的磷酸化,从而减少细胞内DOPA的形成。