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An altered pattern of liver apolipoprotein A-I isoforms is implicated in male chronic hepatitis B progression
Fu Yang1, Yixuan Yin, Fang Wang
1Department of Medical Genetics, Second Military Medical University, Shanghai, China.
Insights
Chronic hepatitis B (CHB) progresses faster in males. Oxidative modification of Apolipoprotein A-I (Apo A-I) in male CHB patients may explain this gender disparity in liver disease progression.
Area of Science:
- Hepatology
- Proteomics
- Molecular Biology
Background:
- Chronic hepatitis B (CHB) exhibits faster progression in males.
- CHB-related liver diseases like cirrhosis and hepatocellular carcinoma predominantly affect men and postmenopausal women.
Purpose of the Study:
- To investigate the molecular mechanisms behind gender disparity in CHB progression.
- To compare liver proteomes between male and female HBV transgenic mice and controls.
Main Methods:
- Two-dimensional difference gel electrophoresis (2D-DIGE) to analyze liver proteomes.
- 2D Western blotting to analyze serum Apolipoprotein A-I (Apo A-I) isoforms.
- Identification of differentially expressed proteins and modified isoforms.
Main Results:
- Identified 8 differentially expressed proteins in male and 12 in female HBV-Tg mice.
- Apolipoprotein A-I (Apo A-I) was downregulated in both male and female HBV-Tg mouse livers.
- Altered Apo A-I isoform patterns were observed in male HBV-Tg mice and male CHB patient sera, linked to oxidative modification.
Conclusions:
- Apolipoprotein A-I (Apo A-I) isoform alterations, specifically oxidative modification, may contribute to the gender disparity in CHB progression.
- Modified Apo A-I isoforms could serve as a pathological hallmark for understanding CHB pathogenesis.
- Further research into gender-specific molecular mechanisms in CHB is warranted.
Abstract:
Chronic hepatitis B (CHB) appears to progress more rapidly in males than in females, and CHB-related hepatic cirrhosis and hepatocellular carcinoma are predominately diseases that tend to occur in men and postmenopausal women. To obtain more insight into the underlying mechanisms of gender disparity of CHB progress, two-dimensional difference gel electrophoresis was employed to compare liver proteome of C57BL/6 and HBV transgenic (HBV-Tg) mice both in male and female groups. We identified 8 differently expressed proteins in male HBV-Tg mice and 12 in female HBV-Tg mice. Apolipoprotein A-I (Apo A-I) was found to be down-regulated in male and female HBV-Tg mouse liver. It is more interesting that the pattern of liver Apo A-I isoforms was altered in male HBV-Tg mice but not in female HBV-Tg mice. Our further results indicated that the basic Apo A-I isoform, based on pI positions from serum 2-dimensional Western blotting, increased in male CHB patient sera but not in female CHB patient sera. Finally, we identified that the oxidative modification Apo A-I mainly reside in basic isoform. This pattern of selectively modified Apo A-I isoforms may be considered as a pathological hallmark that may extend our knowledge of the molecular pathogenesis of CHB progression.
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