Turkish Journal of Biochemistry, cilt.50, sa.5, ss.759-767, 2025 (SCI-Expanded, Scopus)
Calcium/Calmodulin-dependent protein kinase-2 (CaMKII) is a serine/threonine kinase prevalent in neuronal cells, playing a key role in memory, learning, and synaptic plasticity. Nonspecific CaMKII inhibition can prevent apoptosis in neuronal cells and reduce glutamate-induced cell death. Additionally, variations in CaMKK enzyme levels affect hemopoietic stem cell proliferation, although the effects of CaMKII on stem cell responses during stress remain unclear. This study aims to explore CaMKII's impact on the survival and proliferation of mesenchymal stem cells under stress and analyze the expression of its isoforms (alpha, beta, gamma, and delta) in these conditions. The study included the characterization of MSCs, followed by an evaluation of the effects of KN-93, a CaMKII inhibitor, on the viability and proliferation of stem cells both in the presence and absence of H2O2 treatment. The toxicity caused by the application of 1mM H2O2 further increased by inhibitor treatment. Additionally changes in the gene expression levels of CaMKII isoforms were analyzed. The application of H2O2 significantly decreased the total expression levels of CaMKII, with a significant reduction in the delta isoform. Furthermore, CaMKII inhibition by KN-93 increased the toxicity induced by H2O2. Viability and proliferation of stem cells were negatively impacted by the combined treatment of KN-93 and H2O2 compared to H2O2 alone. Our findings provide a strong foundation to understand the response mechanisms of MSCs under stress conditions and could inform strategies for targeted stem cell therapies in oxidative stress conditions.