PMID- 31754242
OWN - NLM
STAT- MEDLINE
DCOM- 20201109
LR  - 20210110
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Nov 21
TI  - Calcium signalling in mammalian cell lines expressing wild type and mutant human 
      alpha1-Antitrypsin.
PG  - 17293
LID - 10.1038/s41598-019-53535-1 [doi]
LID - 17293
AB  - 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 Ca(2+)-signalling, 
      which may contribute to the pathology associated with another serpinopathy, 
      alpha(1)-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 Ca(2+), 
      its responses to thapsigargin (TG), an ER Ca(2+)-ATPase blocker, and 
      store-operated Ca(2+)-entry (SOCE). Our fura2 based Ca(2+) 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 
      alpha1-antitrypsin (AAT) deficiency, unlike the case for FENIB, we were unable to 
      detect defects in calcium signalling.
FAU - Malintan, Nancy T
AU  - Malintan NT
AD  - Centre for Respiratory Biology, UCL Respiratory, Rayne Building, University 
      College London, 5 University Street, London, WC1E 6JF, UK.
AD  - UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
FAU - Buckingham, Steven D
AU  - Buckingham SD
AD  - Centre for Respiratory Biology, UCL Respiratory, Rayne Building, University 
      College London, 5 University Street, London, WC1E 6JF, UK.
FAU - Lomas, David A
AU  - Lomas DA
AD  - Centre for Respiratory Biology, UCL Respiratory, Rayne Building, University 
      College London, 5 University Street, London, WC1E 6JF, UK.
FAU - Sattelle, David B
AU  - Sattelle DB
AD  - Centre for Respiratory Biology, UCL Respiratory, Rayne Building, University 
      College London, 5 University Street, London, WC1E 6JF, UK. d.sattelle@ucl.ac.uk.
LA  - eng
GR  - MR/N024842/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191121
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (SERPINA1 protein, human)
RN  - 0 (alpha 1-Antitrypsin)
RN  - SY7Q814VUP (Calcium)
RN  - Familial encephalopathy with neuroserpin inclusion bodies
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Calcium/*metabolism
MH  - Calcium Signaling/*genetics
MH  - Cricetulus
MH  - Epilepsies, Myoclonic/*genetics/pathology
MH  - Heredodegenerative Disorders, Nervous System/*genetics/pathology
MH  - Humans
MH  - Microscopy, Confocal
MH  - Mutation
MH  - Optical Imaging
MH  - alpha 1-Antitrypsin/genetics/*metabolism
PMC - PMC6872872
COIS- The authors declare no competing interests.
EDAT- 2019/11/23 06:00
MHDA- 2020/11/11 06:00
PMCR- 2019/11/21
CRDT- 2019/11/23 06:00
PHST- 2019/08/26 00:00 [received]
PHST- 2019/10/28 00:00 [accepted]
PHST- 2019/11/23 06:00 [entrez]
PHST- 2019/11/23 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2019/11/21 00:00 [pmc-release]
AID - 10.1038/s41598-019-53535-1 [pii]
AID - 53535 [pii]
AID - 10.1038/s41598-019-53535-1 [doi]
PST - epublish
SO  - Sci Rep. 2019 Nov 21;9(1):17293. doi: 10.1038/s41598-019-53535-1.