Dynamic correlation between induction of the expression of heme oxygenase-1 and hepatitis B viral replication

Shen,Yu‑Ming; Zhang,Hong‑Li; Wu,Yi‑Hang; Yu,Xiao‑Ping; Hu,Hua‑Jun; Dai,Ling‑Hao

doi:10.3892/mmr.2015.3278

Dynamic correlation between induction of the expression of heme oxygenase-1 and hepatitis B viral replication

Authors:
- Yu‑Ming Shen
- Hong‑Li Zhang
- Yi‑Hang Wu
- Xiao‑Ping Yu
- Hua‑Jun Hu
- Ling‑Hao Dai
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Affiliations: Department of Pharmacy, Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, P.R. China
Published online on: January 29, 2015 https://doi.org/10.3892/mmr.2015.3278
Pages: 4706-4712

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Abstract

Heme oxygenase‑1 (HO‑1) possesses significant potential as a drug target for hepatitis B, which may be transferable to patient therapy. The aim of the present study was to clarify the dynamic correlation between the hepatitis B virus (HBV) and HO‑1. The levels of HBV replication and expression of HO‑1 were investigated in HepG2.2.15 hepatoma cells following exposure to 5‑50 µM hemin for 1‑6 days. The mRNA expression levels of HO‑1 were then detected using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). HBV replication levels were determined by enzyme‑immunoassay and a PCR‑fluorescence quantitation assay. The results of the present study demonstrated that the mRNA expression levels of HO‑1 increased in a dose‑dependent manner in the HepG2.2.15 cells, following exposure to 5‑50 µM hemin. The mRNA expression levels of HO‑1 reached a peak following exposure of the cells to hemin for three days, subsequently the expression of HO‑1 decreased. Following exposure to hemin at an optimal concentration of 50 µM for 1‑6 days, the levels of the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the cells were significantly reduced. This marked reduction in the expression of HBsAg and HBeAg reached its peak on the first day, following which the inhibition weakened as the duration of exposure increased. In addition, the inhibition of HBV DNA replication increased with the a longer duration of exposure. Furthermore, HBV DNA levels were significantly decreased following exposure to hemin for 3‑6 days. In conclusion, the present study demonstrated that induced expression of HO‑1 interfered with HBV replication in a dose and time‑dependent manner, implying that a reduction of the HBV viral load may contribute to upregulation in the expression of HO‑1.

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