Methamphetamine induces macropinocytosis in differentiated SH-SY5Y human neuroblastoma cells

Brain Research
Akina NaraKoichi Uemura

Abstract

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 7mM 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 HSP47-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 pro...Continue Reading

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Citations

Mar 21, 2012·Cell Biology and Toxicology·Toshihiko AkiKoichi Uemura
Dec 18, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Annmarie Ramkissoon, Peter G Wells
Apr 15, 2014·The American Journal of Pathology·William A Maltese, Jean H Overmeyer
Jan 30, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Weiye HuangHuijun Wang
Mar 13, 2015·Frontiers in Physiology·William A Maltese, Jean H Overmeyer
Jun 26, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiang XuHuijun Wang
Jun 23, 2016·Oncotarget·Andrey V ShubinSergey V Kostrov
Apr 11, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Cosimo Commisso
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Markus RitterHubert H Kerschbaum

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