Store-operated calcium entry contributes to abnormal Ca2+ signalling in dystrophic mdx mouse myoblasts

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dc.cclicenceCC-BY-NCen
dc.contributor.authorOnopiuk, M.en
dc.contributor.authorBrutkowski, W.en
dc.contributor.authorYoung, Christopher N. J.en
dc.contributor.authorKrasowska, E.en
dc.contributor.authorJakubczyk, J.en
dc.contributor.authorRitso, M.en
dc.contributor.authorWojciechowska, S.en
dc.contributor.authorArkle, Stephenen
dc.contributor.authorZablocki, K.en
dc.contributor.authorGorecki, Dariuszen
dc.date.acceptance2015-01-20en
dc.date.accessioned2017-12-20T09:50:54Z
dc.date.available2017-12-20T09:50:54Z
dc.date.issued2015-02-04
dc.description.abstractSarcolemma damage and activation of various calcium channels are implicated in altered Ca2+ homeostasis in muscle fibres of both Duchenne muscular dystrophy (DMD) sufferers and in the mdx mouse model of DMD. Previously we have demonstrated that also in mdx myoblasts extracellular nucleotides trigger elevated cytoplasmic Ca2+ concentrations due to alterations of both ionotropic and metabotropic purinergic receptors. Here we extend these findings to show that the mdx mutation is associated with enhanced store-operated calcium entry (SOCE). Substantially increased rate of SOCE in mdx myoblasts in comparison to that in control cells correlated with significantly elevated STIM1 protein levels. These results reveal that mutation in the dystrophin-encoding Dmd gene may significantly impact cellular calcium response to metabotropic stimulation involving depletion of the intracellular calcium stores followed by activation of the store-operated calcium entry, as early as in undifferentiated myoblasts. These data are in agreement with the increasing number of reports showing that the dystrophic pathology resulting from dystrophin mutations may be developmentally regulated. Moreover, our results showing that aberrant responses to extracellular stimuli may contribute to DMD pathogenesis suggest that treatments inhibiting such responses might alter progression of this lethal disease.en
dc.funderThis work was supported by the Interreg IV (TC2N) and the Duchenne Parents Project (The Netherlands) grants to DCG, Ph.D. bursary from the Institute of Biomedical and Biomolecular Sciences to CY, the National Science Centre grant number N 301 530338, Poland (to KZ) and the ‘International PhD Studies in Neurobiology’ project (MPD/2009/4) from the Foundation For Polish Science to EK, co-financed from the European Union Regional Development Fund (grant number MPD4-109) to KZ and DCG.en
dc.identifier.citationOnopiuk, M. et al. (2015) Store-operated calcium entry contributes to abnormal Ca2+ signalling in dystrophic mdx mouse myoblasts. Archives of Biochemistry and Biophysics, 569(3), pp.1-9en
dc.identifier.doihttps://doi.org/10.1016/j.abb.2015.01.025
dc.identifier.urihttp://hdl.handle.net/2086/15031
dc.language.isoenen
dc.peerreviewedYesen
dc.projectidMPD/2009/4en
dc.projectidMPD4-109en
dc.projectidN 301 530338en
dc.publisherElsevieren
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.subjectDuchenne muscular dystrophyen
dc.subjectmdxen
dc.subjectMyoblastsen
dc.subjectStore-operated calcium entryen
dc.subjectSTIM1 proteinen
dc.titleStore-operated calcium entry contributes to abnormal Ca2+ signalling in dystrophic mdx mouse myoblastsen
dc.typeArticleen

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