Methamphetamine induces macropinocytosis in differentiated SH-SY5Y human neuroblastoma cells
Methamphetamine induces macropinocytosis in differentiated SH-SY5Y human neuroblastoma cells
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DOI：
10.1016/j.brainres.2010.07.043
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发表时间：
2010-09-17
期刊：
影响因子：
2.9
通讯作者：
Uemura, Koichi
中科院分区：
文献类型：
--
作者：
Nara, Akina;Aki, Toshihiko;Uemura, Koichi
急性和慢性滥用精神兴奋剂药物，如甲基苯丙胺（冰毒），已被认为会导致细胞死亡。特别是由这类药物引起的神经毒性是人类最严重的不良事件之一。虽然甲基苯丙胺对神经细胞的各种影响已经被研究过，但甲基苯丙胺诱导神经毒性的细胞和分子机制仍有待阐明。为了探讨甲基甲醚诱导细胞毒性的机制，我们研究了视黄酸（RA）分化的SH-SY5Y人神经母细胞瘤细胞的细胞学和生化变化。当甲基安非他明浓度大于7 mM时，观察到明显的细胞死亡，但任何浓度的甲基安非他明处理均未观察到caspase依赖性凋亡细胞死亡。甲基肟最显著的细胞形态学影响是形成大的细胞质空泡，这些空泡分别不与GFP-LC3或H5P47-GFP、自噬体和内质网标记物共定位。相反，这些液泡中有许多含有大分子质量的fitc -葡聚糖，并被证实为大脂质体。我们的研究结果表明，甲基甲醚诱导的ra分化的SH-SY5Y人神经母细胞瘤细胞形态学影响涉及巨噬细胞增多，这一过程的过度刺激可能与甲基甲醚引起的细胞毒性有关。(C) 2010 Elsevier B.V.版权所有
Acute and chronic abuses of psychostimulant drugs such as methamphetamine (METH) have been known to cause cell death. In particular, neurotoxicity caused by such drugs is one of the most serious adverse events in humans. Although various effects on neuronal cells caused by METH have been studied, the cellular and molecular mechanisms of METH-induced neurotoxicity remain to be elucidated. To investigate the mechanism of METH-induced cytotoxicity, we studied cytological as well as biochemical changes in retinoic acid (RA)-differentiated SH-SY5Y human neuroblastoma cells. Marked cell death was observed with more than 7 mM METH, although caspase-dependent apoptotic cell death was not observed with any concentration of METH treatment. The most prominent cytomorphological effect by METH was the formation of large cytoplasmic vacuoles which were not colocalized with either GFP-LC3 or H5P47-GFP, autophagosome and ER markers respectively. In contrast, many of these vacuoles incorporated large molecular weight FITC-dextran and were confirmed as macropinosomes. Our results indicate that METH-induced cytomorphological effects on RA-differentiated SH-SY5Y human neuroblastoma cells involve macropinocytosis and the hyperstimulation of this process may be involved in METH-caused cytotoxicity. (C) 2010 Elsevier B.V. All rights reserved.