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Gender associated effects of the ethanolic extracts of Chinese propolis on the hepatic transcriptome in ethanol-treated mice.

ABSTRACT: Objectives:The current study investigated the potential hepatoprotective effects of the ethanolic extracts of Chinese propolis (EECP) on ethanol-induced fatty liver in mice. Materials and Methods:C57BL/6J mice were orally gavaged with 50% ethanol alone or co-administrated with EECP at the dose of 0.2 ml/kg bodyweight for eight weeks. The dose for ethanol was 6 ml/kg bodyweight for the first two experimental weeks, and then increased to 8, 10, and 12 ml/kg bodyweight every two experimental weeks. Alterations in the hepatic transcriptome due to concomitant administration of EECP were investigated using RNA-Seq technique. Results:Our results showed that the main EECP-responsive genes were involved in lipid syntheses, which were significantly down-regulated in both female and male mice co-administrated with EECP. In female mice, these differentially expressed genes (DEGs) were mainly associated with fatty acid biosynthesis. While in male mice, these DEGs were mainly involved in the steroid metabolic process and cholesterol biosynthetic process. Despite the sex-associated responses in lipid metabolism, EECP also exerted other beneficial effects in female mice through modulation of the cytokine-cytokine receptor interaction pathway that helped explaining its hepato-protective effectiveness. Conclusion:Our findings indicated that the mechanism regarding the hepato-protective effects of EECP was gender-dependent, which is worthy of further investigation during the development of therapeutic interventions using EECP to reduce the adverse influences of ethanol.

SUBMITTER: Ye M

PROVIDER: S-EPMC6885388 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Gender associated effects of the ethanolic extracts of Chinese propolis on the hepatic transcriptome in ethanol-treated mice.

Ye Manhong M Xu Mengting M Ding Mengmeng M Ji Chao C Ji Jian J Ji Fubiao F Wei Wanhong W Yang Shengmei S Zhou Bin B

Iranian journal of basic medical sciences 20191001 10

<h4>Objectives</h4>The current study investigated the potential hepatoprotective effects of the ethanolic extracts of Chinese propolis (EECP) on ethanol-induced fatty liver in mice.<h4>Materials and methods</h4>C57BL/6J mice were orally gavaged with 50% ethanol alone or co-administrated with EECP at the dose of 0.2 ml/kg bodyweight for eight weeks. The dose for ethanol was 6 ml/kg bodyweight for the first two experimental weeks, and then increased to 8, 10, and 12 ml/kg bodyweight every two expe ...[more]

PMID: 31998465

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Project description:BACKGROUND: The persimmon Diospyros kaki Thunb. is an important commercial and deciduous fruit tree. The fruits have proanthocyanidin (PA) content of >25% of the dry weight and are astringent. PAs cause astringency that is often undesirable for human consumption; thus, the removal of astringency is an important practice in the persimmon industry. Soluble PAs can be converted to insoluble PAs by enclosing the fruit in a polyethylene bag containing diluted ethanol. The genomic resource development of the persimmon is delayed because of its large and complex genome. Second-generation sequencing is an efficient technique for generating huge sequences that can represent a large number of genes and their expression levels. RESULTS: We used 454 sequencing for the de novo transcriptome assembly of persimmon fruit treated with 5% ethanol (Tr library) and without treatment as the control (Co library) to investigate the genes and pathways that control PA biosynthesis and other secondary metabolites. We obtained 374.6 Mb in clean nucleotides comprising 624,690 and 626,203 clean sequencing reads from the Tr and Co libraries, respectively. We also identified 83,898 unigenes; 54,719 (~65.2%) unigenes were annotated based on similarity searches with known proteins. Up to 14,954 of the unigenes were assigned to the protein database Clusters of Orthologous Groups (COG), 24,337 were assigned to the term annotation database of Gene Ontology (GO), and 45,506 were assigned to 200 pathways in the database of Kyoto Encyclopedia of Genes and Genomes (KEGG). The two libraries were compared to identify the differentially expressed unigenes. The expression levels of genes involved in PA biosynthesis and tannin coagulation were analysed, and some of them were verified using quantitative real time PCR (qRT-PCR). CONCLUSIONS: This study provides abundant genomic data for persimmon and offers comprehensive sequence resources for persimmon research. The transcriptome dataset will improve our understanding of the molecular mechanisms of tannin coagulation and other biochemical processes in persimmons.

Project description:Mitochondrial protein acetylation increases in response to chronic ethanol ingestion in mice, and is thought to reduce mitochondrial function and contribute to the pathogenesis of alcoholic liver disease. The mitochondrial deacetylase SIRT3 regulates the acetylation status of several mitochondrial proteins, including those involved in ethanol metabolism. The newly discovered desuccinylase activity of the mitochondrial sirtuin SIRT5 suggests that protein succinylation could be an important post-translational modification regulating mitochondrial metabolism. To assess the possible role of protein succinylation in ethanol metabolism, we surveyed hepatic sub-cellular protein fractions from mice fed a control or ethanol-supplemented diet for succinyl-lysine, as well as acetyl-, propionyl-, and butyryl-lysine post-translational modifications. We found mitochondrial protein propionylation increases, similar to mitochondrial protein acetylation. In contrast, mitochondrial protein succinylation is reduced. These mitochondrial protein modifications appear to be primarily driven by ethanol metabolism, and not by changes in mitochondrial sirtuin levels. Similar trends in acyl modifications were observed in the nucleus. However, comparatively fewer acyl modifications were observed in the cytoplasmic or the microsomal compartments, and were generally unchanged by ethanol metabolism. Using a mass spectrometry proteomics approach, we identified several candidate acetylated, propionylated, and succinylated proteins, which were enriched using antibodies against each modification. Additionally, we identified several acetyl and propionyl lysine residues on the same sites for a number of proteins and supports the idea of the overlapping nature of lysine-specific acylation. Thus, we show that novel post-translational modifications are present in hepatic mitochondrial, nuclear, cytoplasmic, and microsomal compartments and ethanol ingestion, and its associated metabolism, induce specific changes in these acyl modifications. These data suggest that protein acylation, beyond protein acetylation, contributes to the overall metabolic regulatory network and could play an important role in the pathogenesis of alcoholic liver disease.

Dataset Information

Gender associated effects of the ethanolic extracts of Chinese propolis on the hepatic transcriptome in ethanol-treated mice.

Publications

Gender associated effects of the ethanolic extracts of Chinese propolis on the hepatic transcriptome in ethanol-treated mice.

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