Dataset Information

Role of ammonia for brain abnormal protein glycosylation during the development of hepatitis B virus-related liver diseases.

ABSTRACT:

Background

Ammonia is the most typical neurotoxin in hepatic encephalopathy (HE), but the underlying pathophysiology between ammonia and aberrant glycosylation in HE remains unknown.

Results

Here, we used HBV transgenic mice and astrocytes to present a systems-based study of glycosylation changes and corresponding enzymes associated with the key factors of ammonia in HE. We surveyed protein glycosylation changes associated with the brain of HBV transgenic mice by lectin microarrays. Upregulation of Galβ1-3GalNAc mediated by core 1 β1,3-galactosyltransferase (C1GALT1) was identified as a result of ammonia stimulation. Using in vitro assays, we validated that upregulation of C1GALT1 is a driver of deregulates calcium (Ca²⁺) homeostasis by overexpression of inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) in astrocytes.

Conclusions

We demonstrated that silencing C1GALT1 could depress the IP3R1 expression, an effective strategy to inhibit the ammonia-induced upregulation of Ca²⁺ activity, thereby C1GALT1 and IP3R1 may serve as therapeutic targets in hyperammonemia of HE.

SUBMITTER: Yang J

PROVIDER: S-EPMC8842931 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Role of ammonia for brain abnormal protein glycosylation during the development of hepatitis B virus-related liver diseases.

Yang Jiajun J Yin Mengqi M Hou Yao Y Li Hao H Guo Yonghong Y Yu Hanjie H Zhang Kun K Zhang Chen C Jia Liyuan L Zhang Fan F Li Xia X Bian Huijie H Li Zheng Z

Cell & bioscience 20220214 1

<h4>Background</h4>Ammonia is the most typical neurotoxin in hepatic encephalopathy (HE), but the underlying pathophysiology between ammonia and aberrant glycosylation in HE remains unknown.<h4>Results</h4>Here, we used HBV transgenic mice and astrocytes to present a systems-based study of glycosylation changes and corresponding enzymes associated with the key factors of ammonia in HE. We surveyed protein glycosylation changes associated with the brain of HBV transgenic mice by lectin microarray ...[more]

PMID: 35164881

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Project description:IntroductionProphylactic administration of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs) is the standard treatment for controlling hepatitis B virus (HBV) recurrence after liver transplantation (LT). Since lifelong use of HBIG is expensive and inconvenient and the antibodies level in anti-hepatitis B surface (HBs) is not sustainable and stable, an alternative strategy is to produce anti-HBs antibodies by active immunization. Our present study aimed to prospectively investigate the efficacy and safety of procedural HBV vaccination in transplanted patients.MethodsRecipients who had undergone LT for hepatitis B related liver diseases more than one year before, with no evidence of HBV recurrence or rejection and normal liver function were enrolled. All subjects received the hepatitis B vaccine (40 μg) by intramuscular injection at months 0, 1, 2, 6 and 12 after enrollment with continuous administration of NAs. The liver function and anti-HBs titers were measured before each vaccination and HBIG (400U) was administrated intramuscularly when anti-HBs titer was lower than 30 IU/L during the course. The results of routine blood tests, liver function, concentration of immunosuppressant, and HBV-DNA copies were monitored during the research. After completion of the vaccination procedure, recipients were regarded as responders if their anti-HBs greater than 30 IU/L were maintained for up to six months without using HBIG and vaccine.ResultsTwenty-seven patients were enrolled in this study and the average anti-HBs titer before vaccination was 19.86±14.80 IU/L. The average anti-HBs titer of the nine responders at the end of the follow-up was 57.14±22.75 IU/L, giving an overall response rate of 33.3% (9/27). There were no reports of reactivation of HBV, rejection, severe anaphylaxis or other adverse events. Responders and non-responders showed their significant difference in anti-HBs titers after the fourth vaccination (P<0.01). Moreover, the majority of non-responders (11/18, 63.64%) had high LY/EO rates (lymphocyte number/eosinophil number>15) while most responders (8/9, 88.89%) had low LY/EO rates at the beginning of vaccination (P = 0.019).ConclusionsActive immunization is an effective, cost-saving, and safe method for the prevention of HBV reactivation in patients transplanted for hepatitis B virus related liver diseases. The LY/EO rate may be a valuable indicator in selecting potential recipients for vaccination.

Dataset Information

Role of ammonia for brain abnormal protein glycosylation during the development of hepatitis B virus-related liver diseases.

Background

Results

Conclusions

Publications

Role of ammonia for brain abnormal protein glycosylation during the development of hepatitis B virus-related liver diseases.

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