阿波利波蛋白L1 (APOL1) 风险变体介导的细胞细胞毒性取决于非洲单体型和表面表达
Nidhi Gupta1,2, Bridget Waas1,3, Daniel Austin4
1Department of Discovery Immunology, Genentech, 1 DNA Way, South San Francisco, CA, 94080, USA.
Scientific reports
|February 14, 2024
概括
阿波利波蛋白L1 (APOL1) 风险变体G1和G2通过杀死细胞引起脏疾病. 这种细胞死亡以剂量依赖的方式发生,特别是在非洲本土的EIK亚型中,而不是其他背景.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- APOL1变种G1和G2与脏疾病有关.
- 之前的研究表明,APOL1变异体在受体细胞中充当表面阴离子通道.
- 以前在HEK-293细胞中报告了APOL1风险变异的细胞毒性,但没有验证均表面表达.
研究的目的:
- 为了研究APOL1杂型在APOL1介导病中的作用.
- 为了确定APOL1风险变异是否会以单核型依赖的方式导致 podocyte 死亡.
- 为了比较APOL1变体在具有相同表面表达的相关细胞类型 (podocytes) 中的细胞毒性.
主要方法:
- 诱导的APOL1-G0,G1和G2变异与EIK,KIK和EMR单元类型在可比表面水平的永生 podocytes.
- 评估 podocyte 活力和 (K+) 导电性使用塔 FLIPR.
- 使用Brefeldin A.研究了APOL1表面表达和局部化的作用.
主要成果:
- APOL1 G1 和 G2 变种在 48 小时内导致剂量依赖的 podocyte 死亡,仅限于本土非洲 EIK 单元型.
- 细胞毒性与增加的K+导电性相关.
- 细胞毒性需要APOL1表面表达;细胞质异构体没有毒性.
结论:
- APOL1风险变体G1和G2以剂量和单元型依赖的方式诱导细胞死亡,特别是在EIK单元型中.
- 哈普洛型背景对于APOL1介导的细胞毒性至关重要.
- 这些发现凸显了细胞背景和相同表面表达在研究APOL1病中的重要性.
更多相关视频
07:15Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
414
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
33.8K
相关概念视频
01:20Renal Corpuscle
2.1K
The glomerulus and Bowman's capsule are two essential components of the nephron, which is the functional unit of the kidney. These microscopic structures play a critical role in the process of blood filtration to produce urine.
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
2.1K
02:41Lethal Alleles
15.4K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.4K