Paris Irmgard, Martinez-Alvarado Pedro, Perez-Pastene Carolina, Vieira Marcelo N N, Olea-Azar Claudio, Raisman-Vozari Rita, Cardenas Sergio, Graumann Rebeca, Caviedes Pablo, Segura-Aguilar Juan
Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Santiago, Chile.
J Neurochem. 2005 Mar;92(5):1021-32. doi: 10.1111/j.1471-4159.2004.02931.x.
The role of dopamine in iron uptake into catecholaminergic neurons, and dopamine oxidation to aminochrome and its one-electron reduction in iron-mediated neurotoxicity, was studied in RCSN-3 cells, which express both tyrosine hydroxylase and monoamine transporters. The mean +/- SD uptake of 100 microm 59FeCl3 in RCSN-3 cells was 25 +/- 4 pmol per min per mg, which increased to 28 +/- 8 pmol per min per mg when complexed with dopamine (Fe(III)-dopamine). This uptake was inhibited by 2 microm nomifensine (43%p < 0.05), 100 microm imipramine (62%p < 0.01), 30 microm reboxetine (71%p < 0.01) and 2 mm dopamine (84%p < 0.01). The uptake of 59Fe-dopamine complex was Na+, Cl- and temperature dependent. No toxic effects in RCSN-3 cells were observed when the cells were incubated with 100 microm FeCl3 alone or complexed with dopamine. However, 100 microm Fe(III)-dopamine in the presence of 100 microm dicoumarol, an inhibitor of DT-diaphorase, induced toxicity (44% cell death; p < 0.001), which was inhibited by 2 microm nomifensine, 30 microm reboxetine and 2 mm norepinephrine. The neuroprotective action of norepinephrine can be explained by (1) its ability to form complexes with Fe3+, (2) the uptake of Fe-norepinephrine complex via the norepinephrine transporter and (3) lack of toxicity of the Fe-norepinephrine complex even when DT-diaphorase is inhibited. These results support the proposed neuroprotective role of DT-diaphorase and norepinephrine.
在同时表达酪氨酸羟化酶和单胺转运体的RCSN-3细胞中，研究了多巴胺在铁摄取进入儿茶酚胺能神经元中的作用，以及多巴胺氧化为氨基chrome及其在铁介导的神经毒性中的单电子还原。RCSN-3细胞中100μM 59FeCl3的平均±标准差摄取量为每分钟每毫克25±4 pmol，与多巴胺（Fe(III)-多巴胺）络合时增加到每分钟每毫克28±8 pmol。这种摄取受到2μM诺米芬辛（43%，p<0.05）、100μM丙咪嗪（62%，p<0.01）、30μM瑞波西汀（71%，p<0.01）和2 mM多巴胺（84%，p<0.01）的抑制。59Fe-多巴胺络合物的摄取依赖于Na+、Cl-和温度。当细胞单独与100μM FeCl3孵育或与多巴胺络合时，未观察到对RCSN-3细胞的毒性作用。然而，在100μM双香豆素（一种DT-黄递酶抑制剂）存在下，100μM Fe(III)-多巴胺诱导毒性（44%细胞死亡；p<0.001），这受到2μM诺米芬辛、30μM瑞波西汀和2 mM去甲肾上腺素的抑制。去甲肾上腺素的神经保护作用可以通过以下几点来解释：（1）它与Fe3+形成络合物的能力；（2）Fe-去甲肾上腺素络合物通过去甲肾上腺素转运体的摄取；（3）即使DT-黄递酶被抑制，Fe-去甲肾上腺素络合物也没有毒性。这些结果支持了DT-黄递酶和去甲肾上腺素所提出的神经保护作用。
