Mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells.

Methamphetamine (METH) induces neurodegeneration through damage and apoptosis of dopaminergic nerve terminals and striatal cells, presumably via cross-talk between the endoplasmic reticulum and mitochondria-dependent death cascades. However, the effects of METH on neural progenitor cells (NPC), an i...

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Autores principales:	Changhai Tian, L Charles Murrin, Jialin C Zheng
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e5178fffa218497792b5ca1af34793af
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spelling	oai:doaj.org-article:e5178fffa218497792b5ca1af34793af2021-11-25T06:22:42ZMitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells.1932-620310.1371/journal.pone.0005546https://doaj.org/article/e5178fffa218497792b5ca1af34793af2009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19436752/?tool=EBIhttps://doaj.org/toc/1932-6203Methamphetamine (METH) induces neurodegeneration through damage and apoptosis of dopaminergic nerve terminals and striatal cells, presumably via cross-talk between the endoplasmic reticulum and mitochondria-dependent death cascades. However, the effects of METH on neural progenitor cells (NPC), an important reservoir for replacing neurons and glia during development and injury, remain elusive. Using a rat hippocampal NPC (rhNPC) culture, we characterized the METH-induced mitochondrial fragmentation, apoptosis, and its related signaling mechanism through immunocytochemistry, flow cytometry, and Western blotting. We observed that METH induced rhNPC mitochondrial fragmentation, apoptosis, and inhibited cell proliferation. The mitochondrial fission protein dynamin-related protein 1 (Drp1) and reactive oxygen species (ROS), but not calcium (Ca2+) influx, were involved in the regulation of METH-induced mitochondrial fragmentation. Furthermore, our results indicated that dysregulation of ROS contributed to the oligomerization and translocation of Drp1, resulting in mitochondrial fragmentation in rhNPC. Taken together, our data demonstrate that METH-mediated ROS generation results in the dysregulation of Drp1, which leads to mitochondrial fragmentation and subsequent apoptosis in rhNPC. This provides a potential mechanism for METH-related neurodegenerative disorders, and also provides insight into therapeutic strategies for the neurodegenerative effects of METH.Changhai TianL Charles MurrinJialin C ZhengPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 5, p e5546 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Changhai Tian L Charles Murrin Jialin C Zheng Mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells.
description	Methamphetamine (METH) induces neurodegeneration through damage and apoptosis of dopaminergic nerve terminals and striatal cells, presumably via cross-talk between the endoplasmic reticulum and mitochondria-dependent death cascades. However, the effects of METH on neural progenitor cells (NPC), an important reservoir for replacing neurons and glia during development and injury, remain elusive. Using a rat hippocampal NPC (rhNPC) culture, we characterized the METH-induced mitochondrial fragmentation, apoptosis, and its related signaling mechanism through immunocytochemistry, flow cytometry, and Western blotting. We observed that METH induced rhNPC mitochondrial fragmentation, apoptosis, and inhibited cell proliferation. The mitochondrial fission protein dynamin-related protein 1 (Drp1) and reactive oxygen species (ROS), but not calcium (Ca2+) influx, were involved in the regulation of METH-induced mitochondrial fragmentation. Furthermore, our results indicated that dysregulation of ROS contributed to the oligomerization and translocation of Drp1, resulting in mitochondrial fragmentation in rhNPC. Taken together, our data demonstrate that METH-mediated ROS generation results in the dysregulation of Drp1, which leads to mitochondrial fragmentation and subsequent apoptosis in rhNPC. This provides a potential mechanism for METH-related neurodegenerative disorders, and also provides insight into therapeutic strategies for the neurodegenerative effects of METH.
format	article
author	Changhai Tian L Charles Murrin Jialin C Zheng
author_facet	Changhai Tian L Charles Murrin Jialin C Zheng
author_sort	Changhai Tian
title	Mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells.
title_short	Mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells.
title_full	Mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells.
title_fullStr	Mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells.
title_full_unstemmed	Mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells.
title_sort	mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/e5178fffa218497792b5ca1af34793af
work_keys_str_mv	AT changhaitian mitochondrialfragmentationisinvolvedinmethamphetamineinducedcelldeathinrathippocampalneuralprogenitorcells AT lcharlesmurrin mitochondrialfragmentationisinvolvedinmethamphetamineinducedcelldeathinrathippocampalneuralprogenitorcells AT jialinczheng mitochondrialfragmentationisinvolvedinmethamphetamineinducedcelldeathinrathippocampalneuralprogenitorcells
_version_	1718413833921363968

Mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells.

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