Effects of SRC and IKKβ Kinase Inhibition in Ischemic Factors Modeling In Vitro and In Vivo

Abstract

The search for new molecular targets whose modulation can reduce nerve cell dysfunction and neuronal death during ischemic damage is one of the most significant issues in both fundamental and clinical neurobiology. Various kinase enzymes are often considered to be such promising targets since they are involved in key molecular cascades that regulate cell adaptation to stress factors. Our work is devoted to the study of the role of two kinases—SRC and IKKβ—in maintaining the neural networks’ functional activity under a hypoxic condition in vivo and in vitro. SRC kinase is a cytoplasmic non-receptor protein tyrosine kinase. It is involved in the regulation of cell proliferation and differentiation; its expression in nerve cells changes during hypoxia. IKKβ kinase is involved in the regulation of the activity of the transcription factor NF-κB, which is a pleiotropic regulator of many cellular signaling pathways. We have shown that blockade of SRC and IKKβ kinases by selective inhibitors maintains cell viability in modeling hypoxic damage in vitro but does not allow for the preservation of the bioelectrical activity of neurons. Studies in vivo have shown the neuroprotective effect of SRC but not IKKβ kinase inhibition in the modeling of cerebral ischemia in mice.

Keywords

• kinases
• SRC
• IKKβ
• primary hippocampal cultures
• bioelectrical neural network activity
• hypoxia