氨胺通过抑制自酶诱导HUVEC衰老
Jing Xia1,2, Yu Zhou3, Siyue He1,2
1Department of Human Anatomy Histology and Embryology, School of Basic Medicine, Dali University, 671000 Dali, Yunnan, China.
Discovery medicine
|June 5, 2023
概括
氨胺通过抑制自和激活mTOR通路,诱导人类脉内皮细胞的细胞衰老. 这一发现可能有助于管理阿姆纳菲德.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 由于血液毒性和消化系统问题,阿莫纳菲德 (Amo) 的临床使用有限.
- 化疗的副作用与细胞衰老的增加有关.
- 这项研究研究了阿莫纳菲德在诱导HUVEC老化中的作用及其潜在机制.
研究的目的:
- 为了确定阿莫纳菲德是否会在HUVEC中诱导细胞衰老.
- 阐明阿莫纳菲德导致衰老的分子机制.
- 探索潜在的策略来管理阿莫纳菲德的不良影响.
主要方法:
- 用阿莫纳菲德治疗了HUVEC细胞系.
- 通过SA-β-Gal染色来评估衰老.
- 关键的与衰老相关的蛋白质 (p53,p16) 和自标志物 (AMPK,mTOR,p62,LC3) 通过西式斑块测量得到量化.
- 通过RT-qPCR分析了p53,p21和炎症性细胞因子 (IL-1β,IL-6,IL-8,MCP-1) 的基因表达.
- 使用CCK-8试验测量细胞活力.
主要成果:
- 氨胺增加了SA-β-Gal阳性细胞,p53和p16蛋白质水平.
- 观察到与衰老相关的基因 (p53,p21) 和炎症性细胞因子 (IL-1β,IL-6,IL-8,MCP-1) 的升级.
- 氨胺治疗导致mTOR和p62增加,LC3II/LC3I比率降低,表明自抑制.
- 在0.8微米的度下,阿莫纳菲德显著降低了HUVEC活力.
结论:
- 氨胺在HUVEC中诱导细胞衰老.
- 该机制涉及自抑制和mTOR通路激活.
- 这些发现为管理阿米纳胺诱导的不良反应提供了洞察力.
相关概念视频
Autophagic Cell Death
3.5K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.5K
Autophagy
4.4K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.4K
Delivery Pathways to the Lysosome
6.6K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.6K
Apoptosis
11.6K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
11.6K
Replicative Cell Senescence
3.7K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.7K
Anaphase Promoting Complex
2.9K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K


