Modulation of CaMKII levels in Wharton’s jelly mesenchymal stem cells under hydrogen peroxide induced stress conditions

Abstract Objectives 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. Methods 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 H 2 O 2 treatment. The toxicity caused by the application of 1 mM H 2 O 2 further increased by inhibitor treatment. Additionally changes in the gene expression levels of CaMKII isoforms were analyzed. Results The application of H 2 O 2 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 H 2 O 2 . Viability and proliferation of stem cells were negatively impacted by the combined treatment of KN-93 and H 2 O 2 compared to H 2 O 2 alone. Conclusions 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.