Activation of the calcium/calmodulin-dependent protein kinases as a consequence of oxidative stress

Oxygen radicals have diverse effects on cells. In many cases, exposure to reactive oxygen intermediates (ROI) can induce cell death. Conversely, there is also evidence that suggests oxygen radicals can activate signaling pathways that are thought to prevent cell death. In this review, the authors discuss the finding that hydrogen peroxide and ROI-generating treatments trigger the activation of the calcium/calmodulin-dependent kinases (CaM-kinases), and the potential role this activation has in preventing apoptosis. Evidence is presented that CaM-kinase activation occurs by both calcium dependent- and independent-pathways in response to ROIs. In addition, the idea is discussed that ROIs have the potential to lead to the phosphorylation of calmodulin and through this mechanism potentiate the activation of the CaM-kinases. The concept that inhibition of the CaM-kinases as a mechanism to sensitize cells to the damaging effects of ROIs is also presented. Contrasting these studies, evidence is presented that exposure of the CaM-kinases directly to hydrogen peroxide also has the apparent ability to inhibit their activity.