Calcium/calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous, structurally complex multifunctional protein serine/threonine kinase that plays an important role in cell apoptosis via linking the ER stress and mitochondrial apoptosis pathways. Recently, CaMKII has been correlated with apoptosis signal-regulating kinase 1 (ASK1) activity and the ASK1-dependent apoptosis pathway through the direct phosphorylation of Thr845 of ASK1. The specific role of CaMKII in hypoxia-reoxygenation (H/R)-induced spinal astrocyte apoptosis, however, remains unclear. In this study, we investigated the effects of CaMKIIγ (an isoform of CaMKII) on spinal astrocyte apoptosis using an in vitro oxygen-glucose deprivation (OGD/R) model which mimics hypoxic/ischemic conditions in vivo. OGD/R increased cell death and the activation of CaMKII. Deletion of CaMKIIγ results in the reduced activation of CaMKII and apoptosis in astrocytes under OGD/R conditions. Notably, the deletion of CaMKIIγ induced ASK1 phosphorylation at Thr845 in astrocytes. The activation of JNK and p38 and the downstream effect of ASK1 were also reduced. These data suggest that CaMKIIγ is required for the CaMKII-dependent regulation of ASK1, affecting the apoptosis of a biologically important cell type under spinal cord injury.
This paper investigates the vibration suppression of an elastically supported nonlinear cantilever beam attached to an inertial nonlinear energy sink (NES). The nonlinear terms introduced by the NES are transferred as the external excitations acting on the beam. The governing equations of the nonlinear beam with an inertial NES are derived according to the Lagrange equations and the assumed mode method. The linear and nonlinear frequencies of the beam are numerically obtained by the Rayleigh–Ritz method and the direct iteration method, respectively. The frequencies are verified by the results of the finite element analysis and literature. The responses of the beam under shock excitations and harmonic excitations are numerically solved by the fourth-order Runge–Kutta method. The suppression effect of the inertial NES on the transverse vibration of the beam is evaluated through the values of amplitude reduction and energy dissipation. In addition, a parametric analysis of the inertial NES is conducted to improve the vibration reduction effect of the NES on the beam.
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