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相关概念视频

Cell Specific Gene Expression01:58

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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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cAMP-dependent Protein Kinase Pathways01:25

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Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
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Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
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PPARalpha激活剂抑制了人体单细胞中的组织因子表达和活性.

N Marx1, N Mackman, U Schönbeck

  • 1Department of Internal Medicine II-Cardiology, University of Ulm, Germany. nikolaus.marx@medizin.uni-ulm.de

Circulation
|February 24, 2001
PubMed
概括

过氧体增殖器激活受体α (PPARalpha) 激活剂降低了人体单细胞中的组织因子 (TF) 表达和活性. 这一发现表明了减少动脉样硬化病变中血栓发生力的潜在治疗策略.

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科学领域:

  • 心血管生物学 心血管生物学
  • 分子医学是分子医学.
  • 药理学 药理学是指药理学的学科.

背景情况:

  • 单细胞/巨细胞上的组织因子 (TF) 在急性冠状动脉综合征中启动血栓形成.
  • 过氧体增殖器激活受体-α (PPARalpha) 调节基因表达.
  • PPARalpha激活剂可能会降低患者的TF活性.

研究的目的:

  • 调查PPARalpha激活剂是否可以限制人类单细胞细胞的TF反应.
  • 探索PPARalpha激活剂影响TF表达的机制.

主要方法:

  • 人类单细胞和巨细胞用PPARalpha激活剂 (WY14643,ETYA) 进行治疗.
  • 脂聚糖 (LPS) 用于诱导TF活性和表达.
  • 测量了TF活性,蛋白质,mRNA和促进剂活性.
  • 评估了核因子-kappaB (NF-κB) 的结合和活性.

主要成果:

  • PPARalpha激活剂显著降低了LPS诱导的TF活性和单细胞/巨细胞中的表达.
  • PPARgamma激活剂没有表现出类似的效果.
  • WY14643降低了瘤亡因子-α蛋白,并抑制了LPS诱导的TF促进体活性,可能是通过NF-κB抑制.

结论:

  • PPARalpha激活剂有效地降低了人体单细胞/巨细胞中的TF表达和活性.
  • 这些发现表明PPARalpha激活剂在降低动脉样硬化病变血栓发生性方面可能发挥作用.
  • 这些数据提供了关于PPARalpha激活化合物如何影响动脉瘤的见解.