Calcium signalling in mammalian cell lines expressing wild type and mutant human α1-Antitrypsin

Autor:	David B. Sattelle, David A. Lomas, Nancy T. Malintan, Steven D. Buckingham
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine congenital hereditary and neonatal diseases and abnormalities Thapsigargin Mutant lcsh:Medicine Epilepsies Myoclonic CHO Cells Serpin Article 03 medical and health sciences chemistry.chemical_compound Medical research Cricetulus 0302 clinical medicine medicine Animals Humans Calcium Signaling Familial encephalopathy with neuroserpin inclusion bodies lcsh:Science Calcium signaling Microscopy Confocal Multidisciplinary Chemistry Endoplasmic reticulum Biological techniques Optical Imaging lcsh:R Wild type medicine.disease Cell biology 030104 developmental biology 030228 respiratory system alpha 1-Antitrypsin Mutation Heredodegenerative Disorders Nervous System Calcium lcsh:Q Intracellular
Zdroj:	Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-019-53535-1
Popis:	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.
Databáze:	OpenAIRE
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