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Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.ORCID iD: 0000-0002-7116-0939
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.ORCID iD: 0000-0002-4717-1558
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.ORCID iD: 0000-0001-8279-2790
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0208981Article in journal (Refereed) Published
Abstract [en]

Calcium (Ca2+) is an important ion in physiology and is found both outside and inside cells. The intracellular concentration of Ca2+ is tightly regulated as it is an intracellular signal molecule and can affect a variety of cellular processes. In immune cells Ca2+ has been shown to regulate e.g. gene transcription, cytokine secretion, proliferation and migration. Ca2+ can enter the cytoplasm either from intracellular stores or from outside the cells when Ca2+ permeable ion channels in the plasma membrane open. The Ca2+ release-activated (CRAC) channel is the most prominent Ca2+ ion channel in the plasma membrane. It is formed by ORAI1-3 and the channel is opened by the endoplasmic reticulum Ca2+ sensor proteins stromal interaction molecules (STIM) 1 and 2. Another group of Ca-2(+) channels in the plasma membrane are the voltage-gated Ca2+ (Ca-V) channels. We examined if a change in immunological tolerance is accompanied by altered ORAI, STIM and Ca-V gene expression in peripheral blood mononuclear cells (PBMCs) in pregnant women and in type 1 diabetic individuals. Our results show that in pregnancy and type 1 diabetes ORAI1-3 are up-regulated whereas STIM1 and 2 are down-regulated in pregnancy but only STIM2 in type 1 diabetes. Expression of L-, P/Q-, R- and T-type voltage-gated Ca2+ channels was detected in the PBMCs where the Ca(V)2.3 gene was up-regulated in pregnancy and type 1 diabetes whereas the Ca(V)2.1 and Ca(V)3.2 genes were up-regulated only in pregnancy and the Ca(V)1.3 gene in type 1 diabetes. The results are consistent with that expression of ORAI, STIM and Ca-V genes correlate with a shift in immunological status of the individual in health, as during pregnancy, and in the autoimmune disease type 1 diabetes. Whether the changes are in general protective or in type 1 diabetes include some pathogenic components remains to be clarified.

Place, publisher, year, edition, pages
2018. Vol. 13, no 12, article id e0208981
National Category
Endocrinology and Diabetes Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-372929DOI: 10.1371/journal.pone.0208981ISI: 000453247500057PubMedID: 30543678OAI: oai:DiVA.org:uu-372929DiVA, id: diva2:1277484
Funder
Swedish Research CouncilEXODIAB - Excellence of Diabetes Research in SwedenSwedish Diabetes AssociationSwedish Child Diabetes FoundationErnfors FoundationAvailable from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-10Bibliographically approved

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Bhandage, AmolJin, ZheKorol, Sergiy VTafreshiha, AtiehHellgren, CharlotteEspes, DanielCarlsson, Per-OlaSundström Poromaa, IngerBirnir, Bryndis

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Bhandage, AmolJin, ZheKorol, Sergiy VTafreshiha, AtiehHellgren, CharlotteEspes, DanielCarlsson, Per-OlaSundström Poromaa, IngerBirnir, Bryndis
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