Induction of endoplasmic reticulum-derived oxidative stress by an occult infection related S surface antigen variant.

Abstract

AIM:

To investigate the mechanism of endoplasmic reticulum (ER) stress induction by an occult infection related hepatitis B virus S surface antigen (HBsAg) variant.

METHODS:

We used an HBsAg variant with lower secretion capacity, which was a KD variant from a Korean subject who was occultly infected with the genotype C. We compared the expression profiles of ER stress-related proteins between HuH-7 cells transfected with HBsAg plasmids of a wild-type and a KD variant using Western blot.

RESULTS:

Confocal microscopy indicated that the KD variant had higher levels of co-localization with ER than the wild-type HBsAg. The KD variant up-regulated ER stress-related proteins and induced reactive oxygen species (ROS) compared to the wild-type via an increase in calcium. The KD variant also down-regulated anti-oxidant proteins (HO-1, catalase and SOD) compared to the wild-type, which indicates positive amplification loops of the ER-ROS axis. The KD variant also induced apoptotic cell death via the up-regulation of caspase proteins (caspase 6, 9 and 12). Furthermore, the KD variant induced a higher level of nitric oxide than wild-type HBsAg via the up-regulation of the iNOS protein.

CONCLUSION:

Our data indicate that occult infection related HBsAg variants can lead to ER-derived oxidative stress and liver cell death in HuH-7 cells.

• Authors: In-Kyung Lee, Seoung-Ae Lee, Hong Kim, You-Sub Won, Bum-Joon Kim
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 21 Issue 22 Pg. 6872-83 (Jun 14 2015) ISSN: 2219-2840 [Electronic] United States
• PMID: 26078563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Apoptosis Regulatory Proteins
• Hepatitis B Surface Antigens
• Reactive Oxygen Species

Topics

• Amino Acid Sequence
• Antioxidants (metabolism)
• Apoptosis
• Apoptosis Regulatory Proteins (metabolism)
• Cell Line, Tumor
• Endoplasmic Reticulum (metabolism, pathology, virology)
• Endoplasmic Reticulum Stress
• Gene Expression Profiling
• Genetic Variation
• Genotype
• Hepatitis B Surface Antigens (genetics, metabolism)
• Hepatitis B virus (genetics, metabolism, pathogenicity)
• Hepatitis B, Chronic (metabolism, pathology, virology)
• Hepatocytes (metabolism, pathology, virology)
• Host-Pathogen Interactions
• Humans
• Microscopy, Confocal
• Middle Aged
• Molecular Sequence Data
• Oxidative Stress
• Phenotype
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• Transfection