O-GlcNAcylation在肝脏分化中的重要作用
Dakota R Robarts1, Manasi Kotulkar1, Diego Paine-Cabrera1
1Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA.
Hepatology communications
|November 6, 2023
概括
O-GlcNAcylation对于肝细胞的分化和功能至关重要. 这种修饰的损失会促进肝纤维化和癌症,这表明增加O-GlcNAcylation的疗法可以治疗肝脏疾病.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- O-GlcNAcylation是一种动态的翻译后修饰,调节蛋白质功能.
- 控制O-GlcNAc转移酶 (OGT) 和O-GlcNAcase (OGA) 的控制O-GlcNAcylation水平.
- 失调的O-GlcNAcylation与各种病理状况有关.
研究的目的:
- 研究O-GlcNAcylation在肝细胞分化中的作用.
- 确定改变的O-GlcNAcylation对肝纤维化和肝细胞癌 (HCC) 的影响.
主要方法:
- 使用肝细胞特异性OGT-Knockout (KO) 和OGA-KO小鼠模型.
- 使用单细胞RNA测序来分析肝细胞分化.
- 在甲胺诱导的HCC模型和人类HCC样本中研究了O-GlcNAcylation调制.
主要成果:
- 失去了O-GlcNAcylation破坏了肝脏的区分和肝细胞的分化,影响了糖原的储存和葡萄糖的产生.
- 在OGT-KO小鼠中,HCC发育恶化,炎症,纤维化和YAP信号增加.
- 在OGA-KO小鼠中增加的O-GlcNAcylation抑制了HCC的发展.
- 在人类HCC样本中观察到O-GlcNAcylation的逐渐丧失.
结论:
- O-GlcNAcylation对于维持肝脏分化和预防肝癌发生是必不可少的.
- 改变O-GlcNAcylation水平会影响肝病的进展.
- 增加O-GlcNAcylation对于慢性肝脏疾病,包括HCC,是一个潜在的治疗策略.
相关概念视频
Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K
Oligosaccharide Assembly
2.9K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.9K
Protein Glycosylation
7.0K
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
7.0K
Liver Physiology
585
The liver, an essential organ in the human body, performs over 200 vital functions that can be broadly categorized into metabolic, hematological, endocrine regulation, and bile production.
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
585
Liver Regeneration
3.3K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.3K
Proteoglycans
3.9K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
3.9K


