Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures

We initially identified a nuclear protein, prothymosin-α1 (ProTα), as a key protein inhibiting necrosis by subjecting conditioned media from serum-free cultures of cortical neurons to a few chromatography steps. ProTα inhibited necrosis of cultured neurons by preventing rapid loss of cellular adenos...

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Main Authors:	Ueda, Hiroshi, Fujita, Ryousuke, Yoshida, Akira, Matsunaga, Hayato, Ueda, Mutsumi
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2007
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064059/

id	pubmed-2064059
recordtype	oai_dc
spelling	pubmed-20640592007-11-29 Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures Ueda, Hiroshi Fujita, Ryousuke Yoshida, Akira Matsunaga, Hayato Ueda, Mutsumi Research Articles We initially identified a nuclear protein, prothymosin-α1 (ProTα), as a key protein inhibiting necrosis by subjecting conditioned media from serum-free cultures of cortical neurons to a few chromatography steps. ProTα inhibited necrosis of cultured neurons by preventing rapid loss of cellular adenosine triphosphate levels by reversing the decreased membrane localization of glucose transporters but caused apoptosis through up-regulation of proapoptotic Bcl2-family proteins. The apoptosis caused by ProTα was further inhibited by growth factors, including brain-derived neurotrophic factor. The ProTα-induced cell death mode switch from necrosis to apoptosis was also reproduced in experimental ischemia-reperfusion culture experiments, although the apoptosis level was markedly reduced, possibly because of the presence of growth factors in the reperfused serum. Knock down of PKCβII expression prevented this cell death mode switch. Collectively, these results suggest that ProTα is an extracellular signal protein that acts as a cell death mode switch and could be a promising candidate for preventing brain strokes with the help of known apoptosis inhibitors. The Rockefeller University Press 2007-03-12 /pmc/articles/PMC2064059/ /pubmed/17353361 http://dx.doi.org/10.1083/jcb.200608022 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ueda, Hiroshi Fujita, Ryousuke Yoshida, Akira Matsunaga, Hayato Ueda, Mutsumi
spellingShingle	Ueda, Hiroshi Fujita, Ryousuke Yoshida, Akira Matsunaga, Hayato Ueda, Mutsumi Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures
author_facet	Ueda, Hiroshi Fujita, Ryousuke Yoshida, Akira Matsunaga, Hayato Ueda, Mutsumi
author_sort	Ueda, Hiroshi
title	Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures
title_short	Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures
title_full	Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures
title_fullStr	Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures
title_full_unstemmed	Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures
title_sort	identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures
description	We initially identified a nuclear protein, prothymosin-α1 (ProTα), as a key protein inhibiting necrosis by subjecting conditioned media from serum-free cultures of cortical neurons to a few chromatography steps. ProTα inhibited necrosis of cultured neurons by preventing rapid loss of cellular adenosine triphosphate levels by reversing the decreased membrane localization of glucose transporters but caused apoptosis through up-regulation of proapoptotic Bcl2-family proteins. The apoptosis caused by ProTα was further inhibited by growth factors, including brain-derived neurotrophic factor. The ProTα-induced cell death mode switch from necrosis to apoptosis was also reproduced in experimental ischemia-reperfusion culture experiments, although the apoptosis level was markedly reduced, possibly because of the presence of growth factors in the reperfused serum. Knock down of PKCβII expression prevented this cell death mode switch. Collectively, these results suggest that ProTα is an extracellular signal protein that acts as a cell death mode switch and could be a promising candidate for preventing brain strokes with the help of known apoptosis inhibitors.
publisher	The Rockefeller University Press
publishDate	2007
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064059/
_version_	1611406410938056704

Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures

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