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

In Kyung Lee, Seoung Ae Lee, Hong Kim, You Sub Won, Bum Joon Kim

Research output: Contribution to journalArticle

6 Scopus citations

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 upregulated ER stress-related proteins and induced reactive oxygen species (ROS) compared to the wildtype 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 upregulation 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.

Original languageEnglish
Pages (from-to)6872-6883
Number of pages12
JournalWorld Journal of Gastroenterology
Volume21
Issue number22
DOIs
StatePublished - 14 Jun 2015

Keywords

  • Apoptotic cell death
  • Colocalization
  • Endoplasmic reticulum oxidative stress
  • Hepatitis B virus
  • KD variant
  • Reactive oxidative species

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