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Reactive oxygen species modulates the intracellular level of HBx viral oncoprotein
- Source :
- Biochemical and biophysical research communications. 310(1)
- Publication Year :
- 2003
-
Abstract
- HBx (hepatitis B virus X) viral oncoprotein is a multifunctional protein of which the cellular level may be one of the important factors in determining HBV-mediated pathological progression of liver diseases, chronic hepatitis, and hepatocellular carcinoma. Our previous work revealed that adriamycin, a chemotherapeutic agent, caused a marked increase in the intracellular level of HBx by retarding its rapid degradation. In the present study, modulation of HBx expression was found to be confined to adriamycin but not to other chemotherapeutic agents, cisplatin and 5-fluorouracil. Interestingly, adriamycin caused a rapid increase of reactive oxygen species (ROS) and its accumulation continued until 24h. In contrast, two other agents had little effect on ROS generation, suggesting the possible involvement of ROS in the HBx regulation. In fact, direct addition of H(2)O(2) to the cells significantly increased the level of HBx protein in HBx-expressing ChangX-34 cells as well as in hepatitis B virus-related hepatoma cells, PLC/PRF/5 and HepG2.2.15 cells. Furthermore, antioxidants, N-acetyl-cysteine and pyrrolidinedithiocarbamate (PDTC), completely abolished the increase of HBx protein induced by adriamycin, indicating that adriamycin modulates the intracellular HBx level via ROS generation. Together, these findings provide a novel aspect of HBx regulation by cellular ROS level. Therefore, intracellular microenvironments generating ROS such as severe inflammation may aggravate the pathogenesis of liver disease by accumulating the HBx level.
- Subjects :
- viruses
Biophysics
Biology
Viral Nonstructural Proteins
Biochemistry
Antioxidants
Pathogenesis
Cell Line, Tumor
Gene expression
medicine
Humans
Molecular Biology
Adaptor Proteins, Signal Transducing
Cisplatin
chemistry.chemical_classification
Reactive oxygen species
Signal transducing adaptor protein
Cell Biology
Molecular biology
digestive system diseases
Cell biology
HBx
chemistry
Cell culture
Doxorubicin
Carrier Proteins
Reactive Oxygen Species
Intracellular
medicine.drug
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 310
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....a5c7e270debf94a7ac20efced4a3a824