Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.

The lipid phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P 2), synthesised by PIKfyve, regulates a number of intracellular membrane trafficking pathways. Genetic alteration of the PIKfyve complex, leading to even a mild reduction in PtdIns(3,5)P 2, results in marked neurodegeneration via an uncha...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sally Martin, Callista B Harper, Linda M May, Elizabeth J Coulson, Frederic A Meunier, Shona L Osborne
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f4565a25fa1245668bfee0f210cb289e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f4565a25fa1245668bfee0f210cb289e
record_format	dspace
spelling	oai:doaj.org-article:f4565a25fa1245668bfee0f210cb289e2021-11-18T07:51:42ZInhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.1932-620310.1371/journal.pone.0060152https://doaj.org/article/f4565a25fa1245668bfee0f210cb289e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23544129/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The lipid phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P 2), synthesised by PIKfyve, regulates a number of intracellular membrane trafficking pathways. Genetic alteration of the PIKfyve complex, leading to even a mild reduction in PtdIns(3,5)P 2, results in marked neurodegeneration via an uncharacterised mechanism. In the present study we have shown that selectively inhibiting PIKfyve activity, using YM-201636, significantly reduces the survival of primary mouse hippocampal neurons in culture. YM-201636 treatment promoted vacuolation of endolysosomal membranes followed by apoptosis-independent cell death. Many vacuoles contained intravacuolar membranes and inclusions reminiscent of autolysosomes. Accordingly, YM-201636 treatment increased the level of the autophagosomal marker protein LC3-II, an effect that was potentiated by inhibition of lysosomal proteases, suggesting that alterations in autophagy could be a contributing factor to neuronal cell death.Sally MartinCallista B HarperLinda M MayElizabeth J CoulsonFrederic A MeunierShona L OsbornePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e60152 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sally Martin Callista B Harper Linda M May Elizabeth J Coulson Frederic A Meunier Shona L Osborne Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.
description	The lipid phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P 2), synthesised by PIKfyve, regulates a number of intracellular membrane trafficking pathways. Genetic alteration of the PIKfyve complex, leading to even a mild reduction in PtdIns(3,5)P 2, results in marked neurodegeneration via an uncharacterised mechanism. In the present study we have shown that selectively inhibiting PIKfyve activity, using YM-201636, significantly reduces the survival of primary mouse hippocampal neurons in culture. YM-201636 treatment promoted vacuolation of endolysosomal membranes followed by apoptosis-independent cell death. Many vacuoles contained intravacuolar membranes and inclusions reminiscent of autolysosomes. Accordingly, YM-201636 treatment increased the level of the autophagosomal marker protein LC3-II, an effect that was potentiated by inhibition of lysosomal proteases, suggesting that alterations in autophagy could be a contributing factor to neuronal cell death.
format	article
author	Sally Martin Callista B Harper Linda M May Elizabeth J Coulson Frederic A Meunier Shona L Osborne
author_facet	Sally Martin Callista B Harper Linda M May Elizabeth J Coulson Frederic A Meunier Shona L Osborne
author_sort	Sally Martin
title	Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.
title_short	Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.
title_full	Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.
title_fullStr	Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.
title_full_unstemmed	Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.
title_sort	inhibition of pikfyve by ym-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/f4565a25fa1245668bfee0f210cb289e
work_keys_str_mv	AT sallymartin inhibitionofpikfyvebyym201636dysregulatesautophagyandleadstoapoptosisindependentneuronalcelldeath AT callistabharper inhibitionofpikfyvebyym201636dysregulatesautophagyandleadstoapoptosisindependentneuronalcelldeath AT lindammay inhibitionofpikfyvebyym201636dysregulatesautophagyandleadstoapoptosisindependentneuronalcelldeath AT elizabethjcoulson inhibitionofpikfyvebyym201636dysregulatesautophagyandleadstoapoptosisindependentneuronalcelldeath AT fredericameunier inhibitionofpikfyvebyym201636dysregulatesautophagyandleadstoapoptosisindependentneuronalcelldeath AT shonalosborne inhibitionofpikfyvebyym201636dysregulatesautophagyandleadstoapoptosisindependentneuronalcelldeath
_version_	1718422888238809088

Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.

Ejemplares similares