eprintid: 10087107
rev_number: 16
eprint_status: archive
userid: 608
dir: disk0/10/08/71/07
datestamp: 2019-12-03 12:23:25
lastmod: 2021-10-04 01:24:54
status_changed: 2019-12-03 12:23:25
type: article
metadata_visibility: show
creators_name: Malintan, NT
creators_name: Buckingham, SD
creators_name: Lomas, DA
creators_name: Sattelle, DB
title: Calcium signalling in mammalian cell lines expressing wild type and mutant human α1-Antitrypsin
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: K71
divisions: B07
keywords: Biological techniques, Medical research
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abstract: A possible role for calcium signalling in the autosomal dominant form of dementia, familial encephalopathy with neuroserpin inclusion bodies (FENIB), has been proposed, which may point towards a mechanism by which cells could sense and respond to the accumulation of mutant serpin polymers in the endoplasmic reticulum (ER). We therefore explored possible defects in Ca2+-signalling, which may contribute to the pathology associated with another serpinopathy, α1-antitrypsin (AAT) deficiency. Using CHO K1 cell lines stably expressing a wild type human AAT (MAAT) and a disease-causing polymer-forming variant (ZAAT) and the truncated variant (NHK AAT), we measured basal intracellular free Ca2+, its responses to thapsigargin (TG), an ER Ca2+-ATPase blocker, and store-operated Ca2+-entry (SOCE). Our fura2 based Ca2+ measurements detected no differences between these 3 parameters in cell lines expressing MAAT and cell lines expressing ZAAT and NHK AAT mutants. Thus, in our cell-based models of α1-antitrypsin (AAT) deficiency, unlike the case for FENIB, we were unable to detect defects in calcium signalling.
date: 2019-11-21
date_type: published
official_url: https://doi.org/10.1038/s41598-019-53535-1
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1724848
doi: 10.1038/s41598-019-53535-1
pii: 10.1038/s41598-019-53535-1
lyricists_name: Lomas, David
lyricists_name: Sattelle, David
lyricists_id: DALOM96
lyricists_id: DBSAT61
actors_name: Austen, Jennifer
actors_id: JAUST66
actors_role: owner
full_text_status: public
publication: Scientific Reports
volume: 9
article_number: 17293
event_location: England
citation:        Malintan, NT;    Buckingham, SD;    Lomas, DA;    Sattelle, DB;      (2019)    Calcium signalling in mammalian cell lines expressing wild type and mutant human α1-Antitrypsin.                   Scientific Reports , 9     , Article 17293.  10.1038/s41598-019-53535-1 <https://doi.org/10.1038/s41598-019-53535-1>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10087107/1/s41598-019-53535-1.pdf