Impact of protein kinase CK2 inhibitors on proliferation and differentiation of neural stem cells

Abstract

BackgroundProtein kinases play central roles in cell and tissue development. Protein kinase CK2, an ubiquitously expressed serine/threonine kinase has severe impacts on embryo- and spermatogenesis. Since its role in neurogenesis has so far only been investigated in very few studies, we analysed the role of CK2 in neural stem cells by using two specific inhibitors.MethodsNeural stem cells were isolated from the subventricular zone of neonatal mice, using a neurosphere approach. Proliferation of the neurospheres, as well as their differentiation was investigated with and without inhibition of CK2. Changes in proliferation were assessed by counting the number and measuring the diameter of the neurospheres. Furthermore, the absolute cell numbers within the neurospheres were estimated. Differentiation was induced by retinoic acid in single cells after dissociation of the neurospheres. CK2 was inhibited at consecutive time points after induction of the differentiation process.ResultsCK2 inhibition reduced the amount and size of proliferating neurospheres dose dependently. Adding the CK2 inhibitor CX–4945 at the start of differentiation we observed a dose-dependent effect of CX-4945 on cell viability and glia cell differentiation. Adding quinalizarin, a second CK2 inhibitor, at the start of differentiation led to an elevated level of apoptosis, which was accompanied by a reduced neural differentiation. Adding the CK2 inhibitors at 72 h after the start of differentiation had no effect on stem cell differentiation. Conclusion: Inhibition of CK2 influences early gliogenesis in a time point and concentration dependent manner.General significanceThe use of a CK2 inhibitor significantly affects the neural stem cell niche.

CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic dysregulation in Huntington’s disease

“…Pharmacological inhibition of CK2 in cell cultures expressing amyloid beta (Aβ) reduced Aβ aggregation and the production of pro-inflammatory cytokines and increased cell viability (Rosenberger et al 2016). In neural stem cells from neonatal mice, CK2 inhibition also modulated gliogenesis (Bender et al 2017). CK2 is a highly conserved serine/threonine kinase composed of two regulatory beta (CK2β) and two catalytic subunits, alpha (CK2α) and alpha prime (CK2α’) (Niefind et al 2001, Olsen et al 2006, Pinna 2002, Litchfield 2003).…”

Importance of Protein Kinase and Its Inhibitor: A Review

“…The Bender and colleagues have shown that significant effect on CK2 and it has a proliferation and differentiation of neural stem cells from the sub ventricular region in a sample. They reported that proliferative ability is significantly reduced when the enzyme is inhibited [51]. CK2 inhibition interrupts the neuronal and glial lineages within a three-day time window during differentiation.…”

“…The function of CK2 in the nervous system may be investigated further using these methods. As a result, it was discovered that CK2 plays a role in ion channel organisation and synaptic transmission [51]. CX-4945 [Silmitasertib] is a powerful inhibitor of CK2's kinase function that was developed as an anticancer medication.…”

Role of protein kinase CK2 in antitumor drug resistance

“…CK2 has emerged as a possible regulator of cancer stem cell (CSC) genes [103, 104]. Down-regulation of CK2β in epithelial cells induces the acquisition of stem cell-like properties [105], and CK2 inhibition significantly affects the neural stem cell niche [106]. A major role of CK2 has been found in the functions of glioblastoma brain tumor initiating cells (BTICs) [107].…”