通过SIRT2进行脱乙烯化,可以防止与氨酸突变相关的损伤和氨酸聚合
Jingyuan Sun1,2, Pei Li1, Honglian Gui3
1Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey, USA.
JCI insight
|July 24, 2023
概括
帕瑟诺利德在细胞和小鼠中逆转了质丝的破坏,为中间丝疾病提供了潜在的治疗方法. 这种天然化合物向氨酸乙化,这是氨酸相关疾病的新治疗策略.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 质蛋白 (K) 和中间丝 (IF) 蛋白质的突变会导致人体疾病,如表皮质溶解 (EBS) 和肝损伤.
- 超过70种与FI相关的疾病缺乏有效的向疗法.
研究的目的:
- 为了确定可以纠正突变诱导的质纤维丝断裂的化合物.
- 探索氨酸乙化作为IF相关疾病的治疗标.
主要方法:
- 高通量药物查,以识别正常化氨酸丝干扰的化合物.
- 使用细胞和小鼠模型表达突变质蛋白 (K14-R125C,K18-R90C).
- 研究了SIRT2和烯酸乙化在帕瑟诺利德的保护作用中的作用.
主要成果:
- 在K18-R90C模型中,帕瑟诺利德逆转了质纤维的破坏,并保护了对亡的保护.
- 帕瑟诺利德使K18-R90C的过度乙化正常化,SIRT2上调,SIRT2-克拉关联增加.
- 准氨酸乙化部位或使用尼古丁胺胺单核酸模仿了帕瑟诺利德的保护作用.
- 帕瑟诺利德还可以防止K14-R125C介导的丝在角质细胞中的破坏.
结论:
- 酸乙化是某些酸相关疾病的可用药物点.
- 帕瑟诺利德在质突变引起的疾病中显示出治疗潜力.
- 这项研究突出了中间线索疾病的新治疗途径.
相关概念视频
Nucleotide Excision Repair
3.6K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.6K
Phase II Reactions: Acetylation Reactions
271
Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
271
Sulfur Assimilation
45
Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to...
45
Covalently Linked Protein Regulators
6.9K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.9K
Renewal of Skin Epidermal Stem Cells
2.5K
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
2.5K
DNA Damage can Stall the Cell Cycle
9.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K


