人类大动脉平滑肌细胞的激活被PPARalpha抑制,但不是PPARgamma激活器
1U325 INSERM, Département d'Athérosclérose, Institut Pasteur, Lille, France. Bart.Staels@pasteur-lille.fr
Nature
|July 9, 1998
概括
过氧体增殖器激活受体α (PPARα) 激活剂可减少大动脉光滑肌细胞的炎症,并降低急性阶段蛋白质. 这表明PPARα影响动脉样硬化和静脉复缩过程.
科学领域:
- 分子生物学分子生物学
- 心血管研究的心血管研究.
- 代谢性疾病研究研究.
背景情况:
- 过酶增殖器激活受体 (PPARs) 调节脂质和葡萄糖代谢,影响像失脂症和糖尿病这样的代谢障碍.
- PPARα参与脂肪酸氧化和炎症调节,而PPARγ影响脂肪细胞分化.
- 缺乏PPARα的小鼠表现出长时间的炎症反应,突出了PPARα在炎症中的作用.
研究的目的:
- 研究PPARα在人类大动脉光滑肌细胞 (SMC) 中的作用及其对动脉样硬化和静脉复缩的潜在影响.
- 为了确定PPARα连接体是否可以抑制SMC中的炎症反应.
主要方法:
- 在人类大动脉SMC中分析PPARα的表达.
- 用PPARα和PPARγ配体对SMC进行治疗,以评估炎症标志物.
- 分析PPARα对NF-kappaB信号通路的影响.
- 临床研究评估了费诺纤维酸对高脂血症患者血炎症标志物的影响.
主要成果:
- PPARα在人类大动脉SMC中表达.
- PPARα连接体,但不是PPARγ连接体,抑制IL-6和前列腺素的产生和IL-1诱导的COX-2表达.
- PPARα抑制了NF-kappaB信号,导致COX-2的转录抑制.
- 在超脂血症患者中,费诺纤维酸治疗降低了血IL-6,纤维原和C反应蛋白.
结论:
- PPARα激活剂抑制了大动脉SMC中的炎症反应.
- PPARα的激活会降低血急性阶段蛋白质.
- 血管壁中的PPARα可能在调节动脉样硬化和静脉复缩方面发挥重要作用.
相关概念视频
GPCRs Regulate Adenylyl Cylase Activity
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 cells.
Two...
Two...
Adrenergic Receptors: ɑ Subtype
Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Antihypertensive Drugs: Action of Calcium Channel Blockers
Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
Antihypertensive Drugs: Angiotensin II Receptor Blockers
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
G-Protein Gated Ion Channels
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Sensory organs,...
cAMP-dependent Protein Kinase Pathways
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,...
