甲基醇衍生核酸附物以RAGE-依赖的方式驱动血管功能障碍
Seigmund Wai Tsuen Lai1, Supriyo Bhattacharya2, Edwin De Jesus Lopez Gonzalez1
1Department of Diabetes and Cancer Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Antioxidants (Basel, Switzerland)
|January 22, 2024
概括
甲基醇 (MG) 添加物,像CEdG和CEG一样,是糖尿病病 (DKD) 的生物标志物. 这些导管通过RAGE信号传导驱动内皮功能障碍,这表明它在血管疾病的发展和潜在的治疗点中发挥了作用.
科学领域:
- 生物化学 生物化学
- 血管生物学 血管生物学
- 糖尿病学 糖尿病学
背景情况:
- 糖尿病病 (DKD) 是糖尿病患者死亡的主要原因.
- 内皮细胞功能障碍 (ECD) 是DKD和血管疾病的早期指标和加重因素.
- 甲基醇 (MG) 添加物是已知的1型糖尿病中DKD风险的预测因素.
研究的目的:
- 阐明MG adducts导致血管疾病的机制.
- 调查特定的MG诱导核酸添加物 (CEdG和CEG) 在驱动内皮功能障碍中的作用.
主要方法:
- 人类静脉内皮细胞 (HUVECs) 对CEdG和CEG的暴露.
- 评估内皮功能障碍标记物:单细胞粘附,反应性氧物种 (ROS) 生产和内皮透性.
- 转录组分析以识别功能障碍的签名.
- 对高级糖化终产品 (RAGE) 信号发送的受体作用的评估.
主要成果:
- 在HUVEC中,CEdG和CEG暴露诱导了显著的内皮功能障碍.
- 功能障碍的表型包括单细胞粘附度增加,ROS产量增加,透性增强和平衡力受损.
- 观察到一个功能失调的转录基因签名.
- 抑制细胞内RAGE信号传递减弱了这些有害影响.
结论:
- MG诱导的核添加物 (CEdG和CEG) 积极驱动内皮功能障碍.
- 这些 adducts 通过 RAGE 信号通路运行.
- MG添加物不仅是生物标志物,也是血管疾病进展中的潜在致病原体,提供了新的治疗机会.
关键词:
糖尿病 糖尿病患者 糖尿病患者糖尿病病 糖尿病病它们是内皮细胞的内皮细胞.内皮质功能障碍 在内皮质功能障碍葡萄糖的新陈代谢.糖化糖化是什么?糖化糖化是什么?甲基格里奥克萨尔 (Methylglyoxal) 是一种先进糖化终产品 (RAGE) 的受体.血管疾病是血管疾病.更多相关视频
12:15Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
8.7K
14:22Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development
Published on: April 15, 2013
20.3K
相关概念视频
01:05Proteoglycans
3.9K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
3.9K
01:38Nucleotide Excision Repair
3.5K
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...
3.5K
01:24Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
01:25Mutagenicity and Carcinogenicity
1.3K
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...
1.3K
02:38The Ras Gene
6.2K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
6.2K
01:24Small GTPases - Ras and Rho
4.0K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
4.0K