蛋白C中的Asn384Ser突变与年轻的异卵性男性多部位血栓形成有关
Junwei Yuan1,2, Shijie Zhou1, Xi Wu1
1Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Thrombosis and haemostasis
|April 18, 2025
概括
一种罕见的蛋白C突变 (Asn384Ser) 显著损害了其抗凝固和抗炎功能. 这导致血栓形成风险增加,正如在患有这种遗传改变的年轻男性患者中所见的那样.
科学领域:
- 生物化学 生物化学
- 血液学 血液学 血液学
- 分子生物学分子生物学
背景情况:
- 蛋白C (PC) 是人类的一个至关重要的生理抗凝剂.
- 活性蛋白C (APC) 抑制血栓生成,并具有抗炎性质.
- 在PC中,在患有多部位血栓瘤的患者中发现了一种异构Asn384Ser (N384S) 突变,但其功能影响尚不清楚.
研究的目的:
- 为了研究N384S突变蛋白C的功能性改变.
- 阐明与N384S突变相关的血栓形成的分子机制.
主要方法:
- 重组PC-N384S在哺乳动物细胞中得到表达.
- 使用凝血和抗炎试验进行了功能性表征.
- 试验包括血栓激活,氨基溶解活性,FVa抑制和屏障保护作用.
主要成果:
- PC-N384S表达水平降低到野生类型 (WT) 的7%左右.
- 通过血栓素或血栓素-血栓模块素激活PC-N384S显著受损.
- 减少了APC-N384S的催化效率和氨基溶解活性 (分别为~50%和明显下降).
- APC-N384S的抗凝固和抗炎作用明显受损.
结论:
- Asn384Ser突变显著损害了蛋白C的抗凝和屏障保护功能.
- 这些功能缺陷有助于增加携带异构体N384S突变的个体发生血栓形成的风险.
- 了解这些分子机制对于管理受影响患者血栓形成风险至关重要.
相关概念视频
Translation
140.9K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
140.9K
Sex-linked Disorders
98.1K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
98.1K
X-linked Traits
51.5K
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
51.5K
Mutations
77.3K
Overview
77.3K
Genome-wide Association Studies-GWAS
12.1K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
12.1K
Comparing Copy Number Variations and SNPs
16.7K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
16.7K


