相关实验视频
Updated: Jun 24, 2025

07:18
Intracellular Refolding Assay
Published on: January 24, 2012
14.2K
在压力条件下,Hsp70.1的裂变会导致溶解体细胞死亡
Tetsumori Yamashima1,2, Daria Mochly-Rosen3, Soichi Wakatsuki4
1Department of Psychiatry and Behavioral Science, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Frontiers in molecular biosciences
|June 11, 2024
概括
热冲击蛋白70.1 (Hsp70.1) 通常会稳定溶解体,但4-基-2-非基 (4-HNE) 会导致其分裂. 这导致溶解体破裂和细胞死亡,导致与生活方式相关的疾病.
科学领域:
- 细胞生物学 细胞生物学
- 疾病的分子机制.
- 自和 lysosomal 功能的功能.
背景情况:
- 自,包括伴侣介导的自,通过 lysosomes 降解细胞成分.
- 热冲击蛋白70.1 (Hsp70.1) 对于将货物蛋白贩运到溶酶体和稳定溶酶体膜至关重要.
- 伴侣介导的自和溶酶体完整性的破坏增加了细胞对压力的敏感性.
研究的目的:
- 为了阐明4-基-2-nonenal (4-HNE) 破坏Hsp70.1功能和溶酶体完整性的分子机制.
- 调查Hsp70.1碳化和裂变在溶酶体细胞死亡中的作用.
- 建立Hsp70.1功能障碍,溶酶体损伤和生活方式相关疾病之间的联系.
主要方法:
- 研究了Hsp70.1 (NBD,SBD,LL1) 的结构域及其与载荷和溶酶体组件 (BMP) 的相互作用.
- 研究了内源和外源4-HNE对Hsp70.1在Arg469.1碳化中的影响.
- 评估了4-HNE诱导的Hsp70.1修饰对μ-calpain接入,Hsp70.1裂变和 lysosomal膜完整性的影响.
主要成果:
- 4-基-2-非纳尔 (4-HNE) 在Arg469中诱导Hsp70.1的碳化,改变了它的构型.
- 这种修改促进了在 lysosomal 进入之前在 LL1 链接器上的 Hsp70.1 的 μ-calpain 中介裂变.
- Hsp70.1裂变导致溶酶体膜透/破裂,甲素泄漏,以及随后的溶酶体细胞死亡.
结论:
- 4-基-2-nonenal (4-HNE) 是 Hsp70.1 功能障碍和 lysosomal 细胞死亡的关键调解者.
- 由μ-calpain分裂Hsp70.1是一个关键事件,导致 lysosomal膜损伤.
- 这一途径代表了与生活方式相关疾病的病原发生的重要致病因素.
相关概念视频
Lysosomal Hydrolases
3.8K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.8K
Export of Misfolded Proteins out of the ER
3.6K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K
The Proteasome
829
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
829
Caspases
12.4K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.4K
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Delivery Pathways to the Lysosome
6.3K
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...
6.3K

