甲通过阿里碳水化合物受体介导的DNA损伤诱导心脏缩
Fan Zhang1, Yan Jiang1, PinYi Chen1
1The First Affiliated Hospital, MOE Education Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, China.
The Science of the total environment
|December 2, 2025
概括
甲暴露会通过激活烯碳化合物受体 (AHR) 引起心脏缩,导致DNA损伤和细胞衰老. 抑制AHR或细胞衰老可以防止这些心脏影响.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 心血管研究研究心血管研究
背景情况:
- 甲 (BaP) 是一种与心血管疾病相关的环保多环芳.
- 导致BaP引起心脏毒性的精确机制尚未完全理解.
研究的目的:
- 阐明BaP诱导心脏缩的分子机制.
- 调查酸受体 (AHR) 和细胞衰老在BaP心脏毒性的作用.
主要方法:
- 使用了老鼠H9c2心肌细胞和斑马鱼幼虫模型.
- 评估心脏缩标志物 (细胞大小,基因表达).
- 研究了DNA损伤 (BPDE-DNA附加物,γ-H2AX焦点) 和修复通路 (NER).
- 分析了细胞衰老标志物 (β-galactosidase,p21,Lamin B1) 和相关的信号传递 (AHR,Sirt1).
主要成果:
- 通过AHR-Cyp1a1/Cyp1b1轴,BaP暴露诱导了心脏缩和心肌细胞中的细胞衰老.
- 激活BaP的ARH促进了DNA损伤和抑制了核酸切除修复 (NER).
- AHR激活抑制了Sirt1,可能抑制NER并促进衰老.
- 抑制细胞衰老或AHR/激活Sirt1减弱的BaP诱导的心脏缩在体外和体内.
结论:
- 通过BaP激活AHR,通过DNA损伤,压抑的NER和细胞衰老诱导心脏缩.
- 准AHR途径或细胞衰老为与BaP相关的心血管损伤提供了潜在的治疗策略.
相关概念视频
Physical Properties of Amines
4.1K
Amines with low molecular weight are usually gaseous at room temperature, while those with high molecular weight are liquid or solids in nature. Usually, low molecular weight amines have a rotten fish-like smell. Diamines typically have a pungent smell. For instance, cadaverine and putrescine, depicted in Figure 1, are two molecules responsible for decaying tissue.
4.1K
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
658
Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
658
Aromatic Compounds: Overview
13.3K
In general, the term ‘aromatic’ indicates a pleasant smell or fragrance from fresh flowers, freshly prepared coffee, etc. In the early history of organic chemistry, many benzene derivatives were isolated from the pleasant odor oils of the plants. For example, vanillin was isolated from the oil of vanilla, methyl salicylate from the oil of wintergreen, and cinnamaldehyde from the oil of cinnamon. They all had a pleasant odor; hence the name aromatic was given.
In 1825, Faraday isolated...
In 1825, Faraday isolated...
13.3K
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
418
Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
418
π Electron Effects on Chemical Shift: Aromatic and Antiaromatic Compounds
1.8K
In aromatic compounds, such as benzene, the circulation of (4n + 2) π-electrons sets up a diamagnetic or diatropic ring current around the perimeter of the molecule. This current induces a magnetic field that opposes the external field inside the ring and reinforces it on the outside. The protons in benzene are deshielded and exhibit high chemical shifts in the range 6.5–8.5 ppm. The shielding effect at the center of the ring is evident in complex aromatic molecules, such as...
1.8K
Mutagenicity and Carcinogenicity
1.8K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.8K


