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Enterovirus 71 induces integrin β1/EGFR-Rac1-dependent oxidative stress in SK-N-SH cells: Role of HO-1/CO in viral replication
- Source :
- Journal of Cellular Physiology. 226:3316-3329
- Publication Year :
- 2011
- Publisher :
- Wiley, 2011.
-
Abstract
- 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 a crucial role in defending the body against oxidant-induced injury during inflammatory processes. Therefore, we investigated the induction of HO-1 level in host cells, which may exert a beneficial effect to minimize viral replication in SK-N-SH cells. In this study, we found that enterovirus 71 (EV71) induced the generation of reactive oxygen species (ROS) and activation of NADPH oxidase. EV71-induced ROS generation was mediated through activation of integrin β1, an epidermal growth factor receptor (EGFR), Rac1 and NADPH oxidase which revealed by using selective pharmacological inhibitors or transfection with respective siRNAs. In addition, the reduction of viral load was observed with NADPH oxidase inhibitors (apocynin and diphenyleneiodonium chloride), ROS scavenger (N-acetylcysteine), and transfection with p47(phox) siRNA in Western blot and real-time PCR analyses. Consistently, overexpression of HO-1 attenuated EV71-induced NADPH oxidase/ROS generation and EV71 replication which were abrogated by pretreatment with an HO-1 inhibitor, zinc protoporphyrin IX (ZnPP IX). Moreover, metabolite of HO-1, carbon monoxide (CO), also diminished ROS formation and EV71 replication which were reversed by pretreatment with a CO scavenger (hemoglobin) and a cyclic GMP-dependent protein kinase (PKG) inhibitor (KT5823). These findings suggest that up-regulation of HO-1 exerts as a host cellular defense mechanism against EV71 infection in SK-N-SH cells.
- Subjects :
- rac1 GTP-Binding Protein
Small interfering RNA
Time Factors
Physiology
Clinical Biochemistry
Biology
Transfection
Virus Replication
medicine.disease_cause
Neuroblastoma
chemistry.chemical_compound
Cell Line, Tumor
Cyclic GMP-Dependent Protein Kinases
medicine
Humans
Enzyme Inhibitors
Protein kinase A
Cyclic GMP
chemistry.chemical_classification
Carbon Monoxide
Reactive oxygen species
NADPH oxidase
Integrin beta1
NADPH Oxidases
Free Radical Scavengers
Cell Biology
Molecular biology
Enterovirus A, Human
Up-Regulation
Enzyme Activation
ErbB Receptors
Oxidative Stress
chemistry
Viral replication
Apocynin
biology.protein
RNA Interference
Reactive Oxygen Species
Heme Oxygenase-1
Oxidative stress
Signal Transduction
Subjects
Details
- ISSN :
- 00219541
- Volume :
- 226
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Physiology
- Accession number :
- edsair.doi.dedup.....9272facc6690ba6ffdc2f6ea7ac33683