Enterovirus 71 induces integrin β1/EGFR-Rac1-dependent oxidative stress in SK-N-SH cells: role of HO-1/CO in viral replication.

摘要: Oxidative stress became emerged as a key player in the development and progression of many pathological conditions including virus-induced encephalitis. Heme oxygenase-1 (HO-1) plays crucial role defending body against oxidant-induced injury during inflammatory processes. Therefore, we investigated induction HO-1 level host cells, which may exert beneficial effect to minimize viral replication SK-N-SH cells. In this study, found that enterovirus 71 (EV71) induced generation reactive oxygen species (ROS) activation NADPH oxidase. EV71-induced ROS was mediated through integrin β1, an epidermal growth factor receptor (EGFR), Rac1 oxidase revealed by using selective pharmacological inhibitors or transfection with respective siRNAs. addition, reduction load observed (apocynin diphenyleneiodonium chloride), scavenger (N-acetylcysteine), p47(phox) siRNA Western blot real-time PCR analyses. Consistently, overexpression attenuated oxidase/ROS EV71 were abrogated pretreatment inhibitor, zinc protoporphyrin IX (ZnPP IX). Moreover, metabolite HO-1, carbon monoxide (CO), also diminished formation reversed CO (hemoglobin) cyclic GMP-dependent protein kinase (PKG) inhibitor (KT5823). These findings suggest up-regulation exerts cellular defense mechanism infection