The mammalian SPCA1 and SPCA2 ATPases localize in membranes of the secretory pathway and transport ions of Ca2+ and Mn2+. The role of tissue-specific SPCA2 isoform, highly expressed in lungs, mammary gland and gastrointestinal tract, is poorly understood. To elucidate the function of SPCA2, we studied human colon cancer HCT116 cells, grown under ambient and decreased O2 levels. We found that in contrast with other Ca2+-ATPase isoforms the expression of SPCA2 was up-regulated under hypoxia (3% O2), in both adherent (2D) and spheroid (3D) cultures. In spheroids, experiencing lowest O2 levels (30–50 μM, measured by phosphorescence lifetime imaging microscopy), we observed lower staining with reactive oxygen species (ROS)-specific fluorescent probe, which correlated with increased SPCA2. However, SPCA2 expression was up-regulated in cells exposed to reactive oxygen and nitrogen species donors, and when grown at higher density. We noticed that the culture exposed to hypoxia showed overall increase in S phase-positive cells and hypothesized that SPCA2 up-regulation under hypoxia can be linked to Mn2+-dependent cell cycle arrest. Consequently, we found that SPCA2-transfected cells display a higher number of cells entering S phase. Altogether, our results point at the important role of SPCA2 in regulation of cell cycle in cancer cells.
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August 2016
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A schematic representation of the potential effect (in low intracellular Ca2+ conditions) of the Ca2+-binding, EF-hand-containing cytoskeletal protein EFhd2 on kinesin-mediated transport and actin dynamics in presynaptic compartments. For a detailed overview of the links between EFhd2 and neurodegeneration, see the review by Mielenz and Gunn-Moore in this issue (Volume 473, Issue 16, pages 2429–2437). - PDF Icon PDF LinkFront Matter
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Research Article|
August 11 2016
The Ca2+/Mn2+-transporting SPCA2 pump is regulated by oxygen and cell density in colon cancer cells
James Jenkins;
James Jenkins
*School of Biochemistry and Cell Biology, University College Cork, Western Road, Cork, Ireland
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Dmitri B. Papkovsky;
Dmitri B. Papkovsky
*School of Biochemistry and Cell Biology, University College Cork, Western Road, Cork, Ireland
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Ruslan I. Dmitriev
Ruslan I. Dmitriev
1
*School of Biochemistry and Cell Biology, University College Cork, Western Road, Cork, Ireland
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
May 23 2016
Revision Received:
June 03 2016
Accepted:
June 17 2016
Accepted Manuscript online:
June 17 2016
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2016
Biochem J (2016) 473 (16): 2507–2518.
Article history
Received:
May 23 2016
Revision Received:
June 03 2016
Accepted:
June 17 2016
Accepted Manuscript online:
June 17 2016
Citation
James Jenkins, Dmitri B. Papkovsky, Ruslan I. Dmitriev; The Ca2+/Mn2+-transporting SPCA2 pump is regulated by oxygen and cell density in colon cancer cells. Biochem J 15 August 2016; 473 (16): 2507–2518. doi: https://doi.org/10.1042/BCJ20160477
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