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A. A. Kramerov, A. G. Golub, V. G. Bdzhola, S. M. Yarmoluk, A. V. Ljubimov; Cell Shape Changes Induced by Protein Kinase CK2 Inhibitors in Cultured Human Astrocytes and Vascular Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5384.
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Protein kinase CK2 (CK2) is a key regulator of cell migration, proliferation, differentiation, and tumor growth. CK2 is abundant in retinal astrocytes and its inhibition disrupts retinal neovascularization in a mouse model. In human astrocytes, CK2 co-distributes with GFAP-containing intermediate filaments implying its association with the cytoskeleton. The purpose was to study the effects of various CK2 inhibitors on cell shape of human cultured astrocytes and vascular endothelial cells.
Cultured human embryonic astrocytes (HAST-40), glioma cell line U87MG, human brain microvascular and bovine retinal endothelial cells were used. Specific CK2 inhibitors TBB, TBCA, DMAT (all from Calbiochem), and novel inhibitors (Otava Ltd., Kyiv, Ukraine), 5,6,8-trichloro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid and 2-(4,5,6,7-tetraiodo-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoic acid, were added at 0.01-0.20 mM in medium with 0.5% serum. Western blot analysis was used to examine phosphorylated forms of signaling molecules Akt, ERK and p38MAPK after CK2 inhibitor treatment.
We observed a striking effect of CK2 inhibition on cell morphology. All CK2 inhibitors tested caused dramatic changes in shape and adhesion of cultured cells. Attached cells acquired shortened processes, then rounded up and became prone to detachment from the substratum. The minimal effective inhibitor concentrations were 0.05-0.1 mM. CK2 inhibitor-induced alterations were reversible, but longer treatment or higher inhibitor concentration did cause apoptosis, in line with anti-apoptotic role of CK2. Western blot analyses data on possible involvement of activated signaling molecules in the regulation of cell shape will be presented.
CK2 inhibition induced striking changes in cultured human cells’ shape and cytoskeleton that may underlie the anti-angiogenic effect of CK2 inhibition in vivo. These data may allow for the development of novel anti-angiogenic therapeutic approaches.
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