TY - JOUR
T1 - Store-operated calcium entry contributes to abnormal Ca2+ signalling in dystrophic mdx mouse myoblasts
AU - Onopiuk, Marta
AU - Brutkowski, Wojciech
AU - Young, Christopher
AU - Krasowska, Elżbieta
AU - Rog, Justyna
AU - Ritso, Morten
AU - Wojciechowska, Sylwia
AU - Arkle, Stephen
AU - Zablocki, Krzysztof
AU - Gorecki, Dariusz C.
N1 - NOTICE: this is the author’s version of a work that was accepted for publication in Archives of Biochemistry and Biophysics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Archives of Biochemistry and Biophysics, [VOL 569, (2015)] DOI 10.1016/j.abb.2015.01.025
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Sarcolemma 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.
AB - Sarcolemma 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.
U2 - 10.1016/j.abb.2015.01.025
DO - 10.1016/j.abb.2015.01.025
M3 - Article
SN - 0003-9861
VL - 569
SP - 1
EP - 9
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
ER -