No evidence for cell-to-cell transmission of the unfolded protein response in cell culture.
UPR transmission
cell non-autonomous
endoplasmic reticulum stress
neurodegenerative diseases
proteostasis
unfolded protein response
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
03
05
2019
revised:
31
07
2019
accepted:
12
08
2019
pubmed:
24
8
2019
medline:
26
6
2020
entrez:
24
8
2019
Statut:
ppublish
Résumé
The unfolded protein response (UPR) is one of the major cell-autonomous proteostatic stress responses. The UPR has been implicated in the pathogenesis of neurodegenerative diseases and is therefore actively investigated as therapeutic target. In this respect, cell non-autonomous effects of the UPR including the reported cell-to-cell transmission of UPR activity may be highly important. A pharmaca-based UPR induction was employed to generate conditioned media (CM) from CM-donating neuronal ('donor') cells (SK-N-SH and primary mouse neurons). As previously reported, upon subsequent transfer of CM to naive neuronal 'acceptor' cells, we confirmed UPR target mRNA and protein expression by qPCR and automated microscopy. However, UPR target gene expression was also induced in the absence of donor cells, indicating carry-over of pharmaca. Genetic induction of single pathways of the UPR in donor cells did not result in UPR transmission to acceptor cells. Moreover, no transmission was detected upon full UPR activation by nutrient deprivation or inducible expression of the heavy chain of immunoglobulin M in donor HeLa cells. In addition, in direct co-culture of donor cells expressing the immunoglobulin M heavy chain and fluorescent UPR reporter acceptor HeLa cells, UPR transmission was not observed. In conclusion, carry-over of pharmaca is a major confounding factor in pharmaca-based UPR transmission protocols that are therefore unsuitable to study cell-to-cell UPR transmission. In addition, the absence of UPR transmission in non-pharmaca-based models of UPR activation indicates that cell-to-cell UPR transmission does not occur in cell culture.
Identifiants
pubmed: 31442299
doi: 10.1111/jnc.14856
pmc: PMC7003778
doi:
Substances chimiques
Anti-Bacterial Agents
0
Enzyme Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
208-220Informations de copyright
© 2019 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.
Références
J Biol Chem. 1991 Sep 15;266(26):17067-71
pubmed: 1832668
Annu Rev Immunol. 1994;12:991-1045
pubmed: 8011301
Science. 1993 Nov 12;262(5136):1019-24
pubmed: 7694365
Curr Opin Cell Biol. 2015 Apr;33:102-10
pubmed: 25677685
Cell Metab. 2014 Sep 2;20(3):471-82
pubmed: 25017942
Cell. 2016 Dec 15;167(7):1867-1882.e21
pubmed: 27984733
Biochem Biophys Res Commun. 1975 Jul 8;65(1):248-57
pubmed: 167767
Biotechnol Bioeng. 2013 Aug;110(8):2184-94
pubmed: 23436541
Nat Commun. 2016 Apr 25;7:11386
pubmed: 27109633
Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):1027-32
pubmed: 17209010
EMBO J. 2011 Nov 08;30(23):4701-11
pubmed: 22068051
J Neurochem. 2019 Feb;148(4):516-530
pubmed: 30520047
Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6561-6
pubmed: 21464300
Genes Dev. 2014 Jul 15;28(14):1533-43
pubmed: 25030693
Sci Rep. 2019 Feb 7;9(1):1567
pubmed: 30733486
Mol Cell Biol. 2003 Nov;23(21):7448-59
pubmed: 14559994
Biochem Biophys Res Commun. 2011 Jan 21;404(3):790-5
pubmed: 21168385
J Biol Chem. 2009 Mar 13;284(11):6661-73
pubmed: 19131336
EMBO J. 2004 Jan 14;23(1):169-79
pubmed: 14713949
Science. 2015 Aug 7;349(6248):1255555
pubmed: 26250687
Elife. 2017 Dec 18;6:
pubmed: 29251598
Sci Signal. 2017 Jun 06;10(482):null
pubmed: 28588081
Oncogene. 2016 Jan 21;35(3):269-78
pubmed: 25893303
Cell. 2011 Sep 2;146(5):746-60
pubmed: 21884936
J Neurochem. 2017 Sep;142(6):812-826
pubmed: 28643372
FEBS J. 2018 Mar;285(6):995-1011
pubmed: 29148236
Acta Neuropathol. 2015 Sep;130(3):315-31
pubmed: 26210990
Science. 2011 Nov 25;334(6059):1081-6
pubmed: 22116877
Science. 2017 Sep 8;357(6355):1047-1052
pubmed: 28751470
Cell. 2013 Jun 20;153(7):1435-47
pubmed: 23791175